Lactoferrin and angiogenin compositions and uses thereof

ABSTRACT

Compositions are described which contain lactoferrin and angiogenin. The described compositions are useful in treatment of a variety of conditions, particularly in promoting bone health and relief of menopausal symptoms.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/482,653 filed Jul. 7, 2006 which claims priority to U.S. ProvisionalApplication No. 60/795,871, filed Apr. 28, 2006. Both applications areincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to methods of enhancing thebio-availability of coenzyme Q10, and supporting the cardiovascularsystem, and a composition including coenzyme Q10, lactoferrin and/orangiogenin for use in the described methods, for multi-functional healthapplications.

2. Description of the Related Art

Coenzyme Q10 (CoQ-10) is a fundamental molecule for production ofcellular energy in most living organisms. It is a fat-soluble quinone(chemical nomenclature:2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CAS registry no.303-98-0), structurally similar to vitamin K and known by the namesubiquinone, ubidecarenone, neuquinone, and vitamin-Q.

Although found in all human cells, CoQ-10 occurs at relatively elevatedconcentrations in cells with high energy requirements such as heart,liver, muscle, and pancreas. The total body content of CoQ-10 has beenestimated at 0.5-1.5 g. Normal blood levels range from 0.7-1.0 μg/mL.Human cells synthesize CoQ-10 from the amino acid tyrosine, in aneight-step aromatic pathway, requiring adequate levels of vitamins suchas folic acid, niacin, riboflavin, and pyridoxine. A nutritionaldeficiency in any of these precursors would lead to CoQ-10 deficiency.[Folkers K. Relevance of the biosynthesis of coenzyme Q10 and the fourbases of DNA as a rationale for the molecular causes of cancer and atherapy. Biochem Biophys Res Commun 224:358-61, 1996].

CoQ-10 is located in the inner mitochondrial membrane. It is a cofactorfor at least three mitochondrial enzymes (complexes I, II and III) thatplays a vital role in oxidative phosphorylation. It functions as theonly non-protein component of the electron transport chain (ETC). Thisunique characteristic enables CoQ-10 to move and transfer electronsbetween flavoproteins and cytochromes. Each pair of electrons processedby the ETC must first interact with CoQ10, which is considered thecentral rate-limiting factor for the mitochondrial respiratory chain.Therefore, CoQ10 plays an essential role in adenosine triphosphate (ATP)or biological energy production. [Levin B. Coenzyme Q: clinicalmonograph. Quart Rev Nat Med 3:235-249, 1994; Crane F L, Sun I L, Sun EE. The essential functions of coenzyme Q. Clin Investig 71:S55-59,1993].

CoQ-10 is located in membranes that are in close proximity to theunsaturated lipid chains, to act as a primary scavenger of freeradicals. The concentration of CoQ-10 in many such membranes is high,about 3 to 30 times more than the tocopherol content. Since much of theCoQ-10 in cell membranes is in the quinol form, it works as a potentantioxidant to scavenge free radicals, as well as inhibit lipid andprotein peroxidation. CoQ-10 constantly undergoes oxidation-reductionrecycling. The reduced form readily donates electrons to neutralizeoxidants and displays strongest antioxidant activity. CoQ-10 is the onlyknown naturally occurring lipid-soluble antioxidant that regenerates toits active form in the body. [Quinn P J, et al. Expansion of theantioxidant function of vitamin E by coenzyme Q. Biofactors 9: 149-154,1999]

The membrane stabilizing property of CoQ-10 has been postulated toinvolve the phospholipid-protein interaction that increasesprostaglandin metabolism. CoQ-10 stabilizes myocardial calcium-dependention channels and prevents the depletion of metabolites essential for ATPsynthesis. CoQ-10 also decreases blood viscosity, and improves bloodflow to cardiac muscle in patients with ischemic heart disease.[Rauchova H, et al. Function of coenzyme Q in the cell: Some biochemicaland physiological properties. Physiol Res 44:209-216, 1995; Kato T, etal. Reduction in blood viscosity by treatment with coenzyme Q10 inpatients with ischemic heart disease. Int J Clin Pharmacol Ther Toxicol28:123-126, 1990].

A vital role in the production of cellular energy combined with itspotent antioxidant activity makes CoQ-10 an essential health supplement.Furthermore, its multifunctional properties including vitamin-likeadjuvant activity, protection against age-related degeneration, supportof homeostasis, prophylactic and therapeutic effects against severaldiseases, makes CoQ-10 an important nutraceutical agent.

The benefits of CoQ-10 supplementation are compelling in the protectiveand therapeutic management of cardiovascular health. Several controlledstudies have reported the clinical efficacy of CoQ-10 as a supplementaltherapeutic in the treatment of congestive heart failure (CHF).Myocardial tissue levels of CoQ-10 in CHF patients is about 33% lowerthan control subjects. Accordingly, the severity of symptoms associatedwith CHF and the presence of dilated cardiomyopathy strongly correlatewith the degree of CoQ-10 deficiency. The proposed mechanism of CoQ-10activity to alleviate symptoms of CHF is by a positive inotropic action.Such activity increases the contractile force of the heart and therebyimproves cardiac output. Several conventional CHF therapeutics alsopossess this positive inotropic property, however, an adequate supply ofcellular energy is necessary for optimal contractility of the heart.Failed hearts are ATP deficient; therefore, the reason behind CoQ-10supplementation during CHF therapy is to improve bioenergetics of thecardiac tissue. Furthermore, any improved tolerance to aerobic exerciseis attributed to the ability of CoQ-10 to maintain oxidativephosphorylation and act as a direct cardio-protectant through ATPproduction. In 1974, the Japanese Government has approved CoQ-10 for thetreatment of cardiovascular disease, leading to its use by more than 12million Japanese adults today. In addition, the use of CoQ-10 has alsobeen widely advocated by healthcare professionals throughout the UnitedStates and Europe. [Mortensen S A, et al. Coenzyme Q10—clinical benefitswith biochemical correlates suggesting a scientific breakthrough in themanagement of chronic heart failure. Int J Tiss Reac 12:155-162, 1990;Mortensen S A. Perspectives on therapy of cardiovascular diseases withcoenzyme Q10 (ubiquinone). Clin Investig 71:S116-123, 1993].

Another widespread replenishment of CoQ-10 is in the clinical managementof hypertension associated with deficiencies of succinate dehydrogenaseand CoQ-10 reductase activity. Accordingly, reversal of CoQ-10deficiency by dietary replenishment seems to control hypertension withreductions in systolic and diastolic blood pressure. [Greenberg S,Frishman W H. Coenzyme Q10—A new drug for cardiovascular disease. J ClinPharmacol 30:596-608, 1990; Yamagami T, Shibata W, Folkers K.Bioenergetics in clinical medicine. Studies on coenzyme Q10 andessential hypertension. Res Commun Chem Pathol Pharmacol 11:273-288,1975; Yamagami T, Shibata W, Folkers K. Bioenergetics in clinicalmedicine. VIII. Administration of coenzyme Q10 to patients withessential hypertension. Res Commun Chem Pathol Pharmacol 14:721-727,1976].

Yet another common application of CoQ-10 is as an active adjuvant torectify (balance) coenzyme deficiency that builds-up during long-termusage of certain medications. Lipid-lowering drugs (“statins”) such aslovastatin, simvastatin, pravastatin and gemfibrozil cause a decrease inserum CoQ-10 levels, which might predispose serious cardiovascularconditions. Therefore, it is advisable to use CoQ-10 supplement withprescription of statins, to protect individuals from risks associatedwith cardiac dysfunction. Beta-blockers (drugs that slow down heart rateand lower blood pressure) could also decrease the endogenous CoQ-10levels by inhibition of CoQ-10-dependent enzymes. Also, certain oralhypoglycemic agents such as glyburide, acetohexamide, and tolazamidecould decrease plasma CoQ-10 levels. CoQ-10 supplementation has beenreported to reduce insulin requirements in diabetes mellitus. Therefore,diabetic patients taking CoQ-10 might require dosage adjustments ofhypoglycemic agents. [Kaikkonen J, et al. Determinants of plasmacoenzyme Q10 in humans. FEBS Lett 443:163-166, 1999; Thibault A, et al.Phase I study of lovastatin, an inhibitor of the mevalonate pathway, inpatients with cancer. Clin Cancer Res 2:483-491, 1996; Pepping J.Coenzyme Q. Am J Health-System Pharm 56:519-521, 1999; Kishi T, et al.Bioenergetics in clinical medicine. Studies on coenzyme Q and diabetesmellitus. J Med 7:307-321, 1976].

Generally, individuals intending to boost physiological CoQ-10 levelsconsume this coenzyme as a dietary supplement in various forms, such assoft gels (most popular delivery format), capsules, tablets, powders orliquids. Regular doses of 30-60 mg/day (approximately 1 mg/kg of bodyweight) are generally recommended to prevent CoQ-10 deficiency and tomaintain normal serum concentrations of 0.7-1.0 μg/mL. Therapeutic dosesof 100-200 mg/day are recommended in the treatment of chronic heartdisease. These higher doses may achieve serum concentrations of 2.0-3.0μg/mL, in order to provide a positive impact on cardiovascular health.Divided doses have also been used to minimize adverse effects (if any)when the supplementation exceeds 100 mg/day. [Pepping J. Coenzyme Q10.Am J Health-Syst Pharm 56:519-521, 1999].

The metabolic fate and physiological turnover of CoQ-10 supplementedthrough the diet has not been fully elucidated. Early studies haveindicated that peak levels of CoQ-10 in the plasma are attained within5-10 hours following oral administration. After intestinal absorption,CoQ-10 is initially sequestered by chylomicrons, transferred to theliver and incorporated into the very low density lipoproteins (VLDL).The elimination half-life of CoQ-10 is approximately 34 hours and itsexcretion is primarily through the biliary tract. [Greenberg S, FrishmanW H. Coenzyme Q10: a new drug for cardiovascular disease. J ClinPharmacol 30:596-608, 1990].

Reduced bioavailability due to poor intestinal absorption is a majorlimitation to use CoQ-10 as a health supplement. Several factors in thegastrointestinal milieu such as inflammatory conditions, pH, and mucosalbrush border status markedly influence the CoQ-10 absorption.Accordingly, more than 60% of the orally administered CoQ-10 is excretedin the feces.

Isoprenoid side-chain in the quinone structure makes CoQ-10 an extremelylipophilic molecule. Therefore, when administered in the form of an oilsolution or some kind of water and/or oil suspension or emulsion,lipophilic compounds usually show a poor bioavailability, which resultsin low concentration and a long build-up time of the compound in thesystemic circulation. Therefore, it is highly critical to developeffective methods to overcome this set back, which is inherent toCoQ-10.

Several attempts to reduce the dosage quantities, and enhancebioavailability of CoQ-10 with solubility-enhancing agents have beenreported. For instance, U.S. Pat. No. 4,824,669 describes a soft gelcapsule with CoQ-10 and at least one vegetable oil carrier. This formulaclaims to increase blood basal levels of CoQ-10 to 2.5 g/mL incomparison to 1.6 g/mL from an equivalent 100 mg dose of a dry powderformulation. U.S. Pat. No. 4,483,873 discloses aqueous solutions ofhydrogenated lecithin to increase CoQ-10 bioavailability. U.S. Pat. No.6,045,826 discloses water-soluble compositions of CoQ-10 with a singlesolubilizing agent containing both hydrophobic and hydrophilic moieties.U.S. Pat. Nos. 6,056,971 and 6,441,050 disclose methods to solubilizeCoQ-10 in a softgel, by mixing with an edible polyhydric alcoholsolvent. U.S. Pat. No. 6,300,377 teaches about a CoQ-10 composition thatomits polyhydric alcohol, but includes other agents to help improvesolubility, including a glyceryl ester molecule having one to three C₂to C₇ acyl groups. U.S. Pat. No. 6,623,734 utilizes medium chaintriglycerides or “GelOil SC (a thixatropic gelatine composition)” ascarriers. U.S. Pat. No. 6,740,338 discloses a method to use alipid-soluble reducing agent (eg. ascorbyl palmitate) to maintain CoQ-10in reduced state as ubiqinol for enhanced bioavailability.

While many patents and different formulations claim increasedbioavailability of CoQ-10, the data supporting these claims are ofteninconclusive. Despite the continuing efforts to enhance the chemicalsolubility, the issue of limited intestinal diffusion of CoQ-10continues to plague its applications as a broad-spectrum healthsupplement. There is a global necessity to develop an effective systemto boost the intestinal assimilation of CoQ-10, preferably by activetransport mechanisms, to augment its bioavailability for variouscellular functions.

The physiological consequence of CoQ-10 supplementation intended forcardiovascular support also needs an in-depth scientific evaluation. Inother words, the structure-function compatibility of a CoQ-10replenishment to generate high cellular energy (strong “exogenousfunctional boost”) with a compromised cardiovascular matrix (weak“endogenous structural frame”) such as in an elderly or diseasedindividual requires a careful pharmacological assessment.

It should be noted that the physiological levels of CoQ-10 decline withage, in order to establish a ‘natural balance’ between the bioenergeticsand the cellular degeneration. Plasma CoQ-10 concentration reach peaklevels at 19-21 years of age and plummets down to 65% by age 80. CoQ-10deficiency is prevalent among patients with congestive heart failure(CHF), cardiomyopathy, and chronic obstructive pulmonary disease (COPD).Certain individuals may experience premature decline in CoQ-10 levels orsuffer from a disorder or condition that hinders CoQ-10 synthesis. SuchCoQ-10 deficiencies may develop with long-term drug use while treatingblood disorders such as hyper-lipidemia (eg. statins to reducecholesterol), hypertension (eg. beta-blockers to control bloodpressure), and diabetes (eg. sulfonylurea-type to regulate blood sugar).All of the above clinical conditions are manifested by severe fatigueand lack of energy.

In order to establish a physiological balance between cardiovascularcondition and cellular energy requirements, it is necessary to promoteregeneration of cardiac muscles (“angiogenesis”) and reinforce thevascular tissue (“vasculogenesis”). Therefore, the boosting of cellularenergy with CoQ-10 supplementation, especially during the management ofcardiovascular health, it becomes critically important that theunderlying cellular-matrix is strengthened using in vivo stimulants ofangiogenesis and vasculogenesis. This fundamental approach of‘structure-functional’ balancing of CoQ-10 for human health applicationshas neither been addressed nor reduced to practice by nutritional orpharmaceutical industry so far.

The present invention provides a novel solution that could significantlyinfluence the global perspective of CoQ-10 applications for human andanimal health.

SUMMARY OF THE INVENTION

Embodiments of the invention provide formulations that provide effectiveassimilation of CoQ-10 while supporting angiogenesis and vasculargeneration, particularly in cardiac tissue.

Embodiments of the invention are directed to compositions which includeat least one of CoQ-10, angiogenin (AGN), and one or moremetal-transport proteins. Preferably, the metal-transport protein iscombined with an anionic compound such as a carbonate, a bicarbonate, ora carbonated liquid. Most preferably, the anionic compound isbicarbonate.

In preferred embodiments, the metal-transport protein is one or more oflactoferrin (LF), ovotransferrin or transferrin. Most preferably, themetal-transport protein is lactoferrin.

In preferred embodiments, the amount of CoQ-10 is from 0.1 to 90% byweight and the amount of metal-transport protein is from 0.1 to 90% byweight.

In preferred embodiments, the metal-transport protein such aslactoferrin is complexed to a metal such as copper, iron, zinc,manganese, chromium, aluminum or gallium. Most preferably, thecomposition includes lactoferrin complexed to copper.

In preferred embodiments, the ratio of metal-transport protein:AGNranges between 100:1 to 1:100. More preferably, the ratio ofmetal-transport protein:AGN ranges between 9:1 to 3:1.

In preferred embodiments, the composition may also include an oil, orother suspending agent, flavoring, coloring agents or combinationsthereof. Preferably, the oil is one or more selected from seed oil, fishor marine oil, canola oil, vegetable oil, safflower oil, sunflower oil,nasturtium seed oil, mustard seed oil, olive oil, sesame oil, soybeanoil, corn oil, peanut oil, cottonseed oil, rice bran oil, palm oil,rapeseed oil, palm kernel oil, lupin oil, coconut oil, flaxseed oil, orevening primrose oil.

In preferred embodiments, the composition also includes phospholipids,antioxidants, vitamins, amino acids, proteins, essential minerals,lecithin and derivatives thereof or combinations thereof. Morepreferably, the phospholipid is one or more selected fromDocosahexaenoic acid (DHA), phosphatidyl glycerol, phosphatidylinositol, phosphatidyl serine, phosphatidyl choline, phosphatidylethanolamine, phosphatidic acids, ceramides, cerebrosides,sphingomyelins and cardiolipins. More preferably, the vitamin is one ormore selected from vitamin A, thiamine, niacinamide, pyridoxine,riboflavin, cyanocobalamin, biotin, pantothenic acid, vitamin C, vitaminD, vitamin E, vitamin K and folic acid. More preferably, the mineral isone or more selected from iron, calcium, magnesium, sodium, potassium,copper, chromium, zinc, molybdenum, iodine, boron, selenium, manganese,derivatives thereof and combinations thereof. More preferably, lecithinis present in an amount of 10% to 60% by weight.

In preferred embodiments, the composition also includes L-carnitine,acetyl-L-carnitine or propionyl L-carnitine in an amount of 1% to 50% byweight.

In preferred embodiments, the composition also includes a viable or anon-viable probiotic which is L. acidophilus, L. amylovorus, L.animalis, L. bavaricus, L. brevis, L. bulgaricus, L. casei spp. casei,L. casei spp. rhamnosus, L. crispatus, L. delbrueckii spp. lactis, L.eichmanni, L. fermentum, L. helveticus, L. jensenii, L. kefir, L.paracasei, L. pentosus, L. plantarum, L. reuteri, L. salivarius, L.sake, Leu. cremoris, Leu. lactis; B. adolescentis, B. animalis, B.bifidum, B. breve, B. infantis, B. longum, and B. thermophilum; Ped.acidilactici, Ped. pentosus, Pep. assacharolyticus, Pep. productus; Pro.acidipropionici, Pro. freudenreichii, Pro. jensenii, Pro. theonii,Strep. cremoris, Strep. faecium, Strep. lactis, Strep. raffinolactis orStrep. thermophilus.

Embodiments of the invention are directed to methods of preparing aLF:AGN premix which includes one or more of the following steps:

-   -   isolating a LF-enriched fraction from a dairy, a non-dairy or a        recombinant source;    -   isolating an AGN-enriched fraction from a dairy, a non-dairy or        a recombinant source;    -   combining the LF-enriched fraction with the AGN-enriched        fraction;    -   freeze-drying or spray-drying the combined fractions; and    -   milling the freeze-dried or spray-dried combined fractions to        obtain a LF:AGN premix.

Embodiments of the invention are directed to LF:AGN premix compositions,including those produced by the above method.

In preferred embodiments, the ratio of LF to AGN is 9:1. Morepreferably, the ratio of LF to AGN is 6:1. Yet more preferably, theratio of LF to AGN is 3:1.

Embodiments of the invention are directed to methods of maintaining goodhealth or treating a disease condition by administering any of thecompositions described above to an individual.

A preferred embodiment is directed to a formulation for vascular healthwhich includes CoQ-10, angiogenin, at least one metal-transport protein,and at least two of the following ingredients: acetyl L-carnitine,vitamin B6, Vitamin E, Selenium, Copper and Flaxseed oil.

A preferred embodiment is directed to a formulation for sports nutritionwhich includes CoQ-10, angiogenin, at least one metal-transport protein,and at least two of the following ingredients: one or more B vitamins,vitamin C, vitamin E, glutamine, taurine, N-acetyl-creatine,N-acetyl-cysteine, one or more L amino acids, acetyl L-carnitine, sodiumand potassium salts, selenium, magnesium, copper, and chromium.

A preferred embodiment is directed to a formulation to promote tissuerecovery after exercise which includes CoQ-10, angiogenin, at least onemetal-transport protein and at least two of the following ingredients:soy lecithin, vitamin B6, vitamin E, selenium, copper, L-taurine,N-acetyl creatine, Dehydroepiandrosterone (DHEA), and one or more aminoacids.

Embodiments of the invention are directed to a protein powder, a sportsbeverage, a carbonated beverage and/or a meal replacement health barwhich include CoQ-10, angiogenin, at least one metal-transport proteinor any of the formulations as described. A preferred embodiment isdirected to a method of preparing a tonic to support muscle building bymixing a protein powder containing CoQ-10, angiogenin, at least onemetal-transport, or one of the formulations described with a food orbeverage.

A preferred embodiment is directed to a formulation for reducing orpreventing vascular plaque which includes CoQ-10, angiogenin, at leastone metal-transport protein and at least two of the followingingredients: pantethine, one or more plant antioxidants, L-carnitine,and red yeast rice.

A preferred embodiment is directed to a formulation for the treatment ofsymptoms of premenstrual syndrome which includes CoQ-10, angiogenin, atleast one metal-transport protein and at least two of the followingingredients: γ-linolenic acid, evening primrose oil, chaste treeextract, one or more B vitamins, folic acid, biotin, calcium andmagnesium.

A preferred embodiment is directed to a formulation for the treatment ofday-time symptoms of perimenopause which includes CoQ-10, angiogenin, atleast one metal-transport protein and at least two of the followingingredients: vitamin B6, vitamin E, vitamin C, selenium, calcium,magnesium, potassium, black cohosh, and red clover. In a preferredembodiment, day-time symptoms of perimenopause are treated byadministering an effective amount to an individual in need thereof.

A preferred embodiment is directed to a formulation for treatingnight-time symptoms of perimenopause which includes CoQ-10, angiogenin,at least one metal-transport protein and at least two of the followingingredients: vitamin B5, vitamin E, vitamin C, selenium, calcium,magnesium, potassium, gamma-oryzanol, L-theanine, and valerian root. Ina preferred embodiment, night-time symptoms of perimenopause are treatedby administering an effective amount to an individual in need thereof.

A preferred embodiment is directed to a formulation for treatingsymptoms of menopause which includes CoQ-10, angiogenin, at least onemetal-transport protein and at least two of the following ingredients:α-linolenic acid, vitamin D, S-adenosylmethionine,methylsulfonylmethane, calcium, magnesium and chromium.

A preferred embodiment is directed to a vaginal suppository for treatingan infection of bacterial, fungal or parasitic origin which includesCoQ-10, angiogenin, at least one metal-transport protein and a probioticmicroorganism.

A preferred embodiment is directed to a formulation for bone healthwhich includes CoQ-10, angiogenin, at least one metal-transport proteinand at least two of the following ingredients: chondroitin sulfate,glucosamine sulfate, methylsulfonylmethane, S-adenosylmethionine,dimethylglycine, and cerasomal-cis-9-cetylmyristoleate.

A preferred embodiment is directed to a formulation for oral hygienewhich includes CoQ-10, angiogenin, and at least one metal-transportprotein.

A preferred embodiment is directed to a formulation for topical use inan acceptable carrier which includes CoQ-10, angiogenin, and at leastone metal-transport protein.

A preferred embodiment is directed to a formulation for decreasing thefrequency of migraine attack which includes CoQ-10, angiogenin, at leastone metal-transport protein, magnesium and riboflavin.

A preferred embodiment is directed to a formulation for enhancing malevirility which includes CoQ-10, angiogenin, at least one metal-transportprotein and at least two of the following ingredients: damiana extract,sarsaparilla extract, saw palmetto, and acetyl-L-carnitine.

A preferred embodiment is directed to a formulation for increasingfemale libido which includes CoQ-10, angiogenin, at least onemetal-transport protein and at least two of the following ingredients:lysozyme, cranberry extract, L-theanine, Echinacea, acetyl-L-carnitine,and tyrosine.

A preferred embodiment is directed to a formulation for brain health andstress management which includes CoQ-10, angiogenin, at least onemetal-transport protein and at least two of the following ingredients:phosphatidyl serine, phenylalanine, one or more B vitamins, vitamin E,taurine, choline, copper and chromium.

A preferred embodiment is directed to a formulation for colon cleansingwhich includes CoQ-10, angiogenin, at least one metal-transport proteinand at least two of the following ingredients: at least one probiotic,cascara sagrada, peppermint oil, gingerol oil, fennel oil, andchlorella.

A preferred embodiment is directed to a formulation for liver cleansingwhich includes CoQ-10, angiogenin, at least one metal-transport protein,milk thistle and dandelion.

A preferred embodiment is directed to a formulation for blood cleansingwhich includes CoQ-10, angiogenin, at least one metal-transport proteinand at least two of the following ingredients: burdock root extract,rosemary leaf extract, red clover extract and yarrow.

A preferred embodiment is directed to a powdered drink formulation whichincludes CoQ-10, angiogenin, at least one metal-transport protein,golden seal, and echinacea. More preferably, the powdered drinkformulation also includes one or more selected from ginger root extract,vitamin C, peppermint, grapefruit seed extract, licorice root extract,cranberry extract, elder, and L-theanine.

Embodiments of the invention are directed to methods of treating a anage-related or physiological Coenzyme Q-10 deficiency, and/or adeficiency condition resulting from long-term drug use in the clinicalmanagement of hypertension, hyperlipidemia and diabetes mellitus, byadministering a composition which includes CoQ-10, angiogenin, and atleast one metal-transport protein at an effective dosage to anindividual in need thereof.

Embodiments of the invention are directed to a method of soft gelencapsulation of compositions which include CoQ-10 and angiogenin, wherethe gel material is one or more selected from bovine gelatin, fishgelatin, lecithin, fatty acids, oils and waxes.

Further aspects, features and advantages of this invention will becomeapparent from the detailed description of the preferred embodimentswhich follow.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

While the described embodiment represents the preferred embodiment ofthe present invention, it is to be understood that modifications willoccur to those skilled in the art without departing from the spirit ofthe invention. The scope of the invention is therefore to be determinedsolely by the appended claims.

One object of the present invention is to provide a natural deliverysystem for active transport of orally administered CoQ-10 across theintestinal mucosa. A further object of the present invention is toprovide a high degree of CoQ-10 bio-availability in the bloodcirculation for its multi-functional assimilation in the body.

Another object of the present invention is to provide an effectivecardiovascular reinforcement system to cope with the cellular energysynthesis anticipated by the bio-available CoQ-10 supplemented by oraladministration.

The objectives of the present invention have been accomplished byincorporating into the CoQ-10 formulations, two nutraceutical milkproteins, namely, “lactoferrin (LF)”, the body's own transportationsystem and “angiogenin (AGN)”, the body's own growth factor thatregulates regeneration of vascular tissue.

Lactoferrin (LF) is the fundamental glycoprotein that plays a key rolein the transport and absorption of nutrients into the blood stream,crossing the intestinal mucosal barrier. Accordingly, LF is equippedwith unique molecular structure and a classic functional mechanism foractive transport and physiological mobilization of iron, zinc, copper,manganese, chromium, aluminum, gallium and several other vital nutrientsfor metabolic assimilation. Furthermore, LF also elicits a powerfulprotective role in the intestinal tract by eliminating harmfulpathogens, toxic chemicals, heavy metals, and free radicals. Specificreceptors in the human duodenal brush border are involved in promotingLF interaction and function during the elemental absorption and nutrienttransport. These LF-binding receptors exist relatively at a high density(about 4 billion sites/microgram) on the human intestinal brush-bordermembrane to facilitate uninterrupted active transport and processing ofnutrients into the circulatory system. [Naidu A S. Lactoferrin—NaturalMultifunctional Antimicrobial, CRC Press/Boca Raton, pp. 1-86, 2000; Coxet al., Iron-binding proteins and influx of iron across the duodenalbrush border. Evidence for specific lactotransferrin receptors in thehuman small intestine. Biochem Biophys Acta 588:120-8, 1979; Kawakami H,Lonnerdal B, Isolation and function of a receptor for human lactoferrinin human fetal intestinal brush-border membranes. Am J Physiol261:G841-6, 1991].

In general, low molecular weight molecules such as ions and metabolites(possibly CoQ10) cross the gut lumen through “passive diffusionprocesses” facilitated by membrane channels in the lumen. Whereas,orally administered LF could pass into the systemic circulation as anintact molecule by two distinct pathways: i) by non-selectivetranscytosis and ii) by specific receptor-mediated transcytosis. LF isknown to bind and potentiate active transport of several moleculesacross membrane barriers. The pharmaco-kinetics of LF absorption in theintestinal tract is fast and reaches a peak level in plasma within 2-h.Furthermore, LF is also rapidly eliminated from the plasma with a meanfractional catabolic rate of 5.7/day, by liver and spleen. [Takeuchi T,et al. Evidence of lactoferrin transportation into blood circulationfrom intestine via lymphatic pathway in adult rats. Exp Physiol89:263-270, 2004].

Therefore, presence of supplemented LF in the intestinal milieu, eitherin free form or complexed to CoQ-10 could facilitate an active transportof several low molecular weight molecules across the intestinal brushborder epithelia. The present invention takes advantage of this basicprinciple in facilitating the transport of CoQ-10 across the intestinallumen into the blood stream. [Naidu A S. Arnold R R. Lactoferrininteraction with Salmonellae potentiates the antibiotic susceptibilityin vitro. Dign Microbiol Infect Dis 20:69-75, 1994].

LF is a 79-kDa glycoprotein present in every mucosal secretion of thehuman body. LF occurs in two major reservoirs, a circulatory pool storedin the neutrophils and a stationary pool covered on the mucosalsurfaces. In the neutrophils, LF is associated with the secondary(specific) granules at a concentration of about 15 μg/10⁶ cells and isreleased isochromously with other lysosomal proteins into the plasmaduring phagocytosis. The concentration of LF in human plasma is about0.2 to 1.5 μg/mL, the values are comparatively lower in women than inmen. Notably, LF is a powerful nutraceutical with well establishedantimicrobial, antioxidant, anti-inflammatory, immuno-modulatory, andprebiotic properties. Furthermore, the iron-binding property of LF isknown to play a vital role in the CoQ-10/Cytochrome (iron-containingcompounds)-mediated bioenergetic pathways [review: Naidu A S.Ultra-cleansing of lactoferrin—nutraceutical implications. AgroFoodIndustry hi-tech 16:7-13, 2005].

Angiogenesis and vasculogenesis are two primary pathways in thedevelopment and maintenance of mammalian health. The angiogenic role isto supply and support tissue with ample vasculature, thus providing aroute of access for the transportation of essential nutrients, includingoxygen and the removal of metabolic waste in a sustained manner.Angiogenesis is a strictly regulated, multi-step process that occursduring normal physiology such as wound healing, pregnancy, anddevelopment.

In preferred embodiments, the coenzyme Q-10 compositions include anagent that promotes angiogenesis and/or vasculogenesis. Such agentsinclude, but are not limited to angiogenin, vascular endothelial growthfactor (VEGF), fibroblast growth factor-acidic (FGF-a), fibroblastgrowth factor-basic (FGF-b), tumor necrosis factor (TNF)-α, andtransforming growth factor (TGF)-α/β. In a preferred embodiment, theangiogenic/vasculogenic agent is angiogenin.

Angiogenin (AGN) has been shown to be a key mediating factor in theunderlying cascade of chemical events leading to angiogenesis, whichmakes it a very important precursor molecule for both muscle developmentand vascular generation. AGN is a 14-kDa, basic heparin-binding proteinand a member of the pancreatic ribonuclease superfamily. AGN resemblespancreatic ribonuclease A; their amino acid sequences are about 35%identical, including the active site residues. [Strydom D J. Theangiogenins. Cell Mol Life Sci 54:811-824, 1998; Acharya B, et al.Crystal structure of human angiogenin reveals the structural basis forits functional divergence from ribonuclease. Proc Natl Acad Sci USA91:2915-2919, 1994].

AGN is present in milk and circulates in human plasma at a concentrationof about 0.3 μg/mL. Its turnover rate is very fast, with a half-life <5min. AGN can induce most of the events necessary for the formation ofnew blood vessels. It binds avidly to endothelial cells and stimulatescell migration and invasion. AGN promotes cell proliferation anddifferentiation; mediates cell adhesion and activates cell associatedproteases; and also induces plasminogen activator and thereby, theplasmin system promoting migration and tubular morphogenesis ofendothelial cells. Exogenous AGN is transported into the nucleus ofendothelial cells. The nuclear translocation results in accumulation ofthe AGN in the nucleolus. Transportation of AGN from the cell surfaceinto the nucleus and subsequently to the nucleolus is critical for itsangiogenic activity. The import of AGN from the cytosol to the nucleusis signal-dependent, carrier mediated and energy-dependent, activetransport process. [Hu G F, Riordan J F, Vallee B L. A putativeangiogenin receptor in angiogenin-responsive human endothelial cells.Proc Natl Acad Sci USA 94:2204-2209, 1997; Moroianu J, Riordan J F.Nuclear translocation of angiogenin in proliferating endothelial cellsis essential to its angiogenic activity. Proc Natl Acad Sci USA91:1677-1681, 1994].

The present invention relates to novel compositions comprising effectiveamounts of CoQ-10. In preferred embodiments, CoQ-10 is provided in acomposition that also includes an agent that promotes angiogenesisand/or vasculogenesis. In preferred embodiments, the agent to supportangiogenesis and/or vasculogenesis is angiogenin. Effective amounts ofangiogenin in the formulation reinforce the cardiovascular framework tocope with the bioenergetic functions of CoQ-10 supplementation. Inpreferred embodiments, the composition includes an amount of LFeffective to bind and transport CoQ-10 into the blood stream, preferablyacross the intestinal mucosa.

Compositions according to the present invention may be used fortreatment of cardiovascular ailments and diseases such as congestiveheart failure, cardiomyopathy; for supportive supplementation oflong-term medications in the management of hypertension, hyperlipidemia,diabetes, and chronic fatigue syndrome; mitochondrial diseases includingmitochondrial encephalomyopathy, lactic acidosis, and stroke-likesymptoms, Keams-Sayre syndrome and Alper' disease;

Definition of Terms

Coenzyme Q10: As used herein, “coenzyme Q10” or “CoQ-10” refers tofat-soluble quinone (chemical name:2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone; CAS registry no.303-98-0), structurally similar to vitamin K. Coenzyme Q10 is also knownby the names ubiquinone, ubidecarenone, neuquinone and vitamin-Q.Coenzyme Q10 used herein also includes different forms of CoQ-10, forexample: reduced CoQ-10, semi-reduced CoQ-10, and genetically orchemically modified CoQ-10. As used herein, coenzyme Q10 used hereinalso refers to “coenzyme Q10 blends” described in the present invention.

Coenzyme Q10 blend: As used herein, “coenzyme Q10 blend” or CoQ-10blend” refers to mixtures of CoQ-10 with LF and AGN; all combined orindividually at varying ratios, eg. CoQ-10, LF and AGN; CoQ-10 and LF;as well as, CoQ-10 and AGN.

Metal-transport proteins: As used herein, “metal-transport proteins”refers to compounds belonging to transferrin super-family. Lactoferrin,transferrin, ovo-transferrin (synonym: conalbumin) andmelano-transferrin.

Lactoferrin: As used herein, “lactoferrin”, or “LF” refers to variousprotein preparations and forms, including but not limited to,lactoferrin-(tcr) (as described in Naidu U.S. Pat. Appl. No.20050197495, published Sep. 8, 2005), freely-dispersed native(fdn)-lactoferrin which includes metal-saturated (holo), partiallysaturated and metal-free (apo) forms of LF. The LF-bound metal ispreferably copper, and other bound metals include zinc, iron, manganese,chromium, aluminum and gallium. The term LF further refers to fully andpartially glycosylated polypeptide chains of LF, incomplete polypeptidechains including half-molecules comprising C- and N-terminus lobes ofLF. The term LF categorically excludes aggregated-LF and immobilized(Im)-LF forms (as described in Naidu U.S. Pat. No. 6,172,040 B1, issuedJan. 9, 2001) that are devoid of any (fdn)-LF.

Freely-dispersed native lactoferrin: As used herein, “freely-dispersednative (fdn)-lactoferrin” or “(fdn)-LF” refers to isolated LF proteinmolecules free of auto-aggregation or polymerization and free frombinding or immobilization to other substrates.

Angiogenic stimulators: As used herein, “angiogenic stimulators” refersto growth factors that stimulate neogenesis and regeneration of vasculartissue including the cardiac muscles. These growth factors include, butnot limited to, angiogenin, vascular endothelial growth factor (VEGF),fibroblast growth factor-acidic (FGF-a), fibroblast growth factor-basic(FGF-b), tumor necrosis factor (TNF)-α, and transforming growth factor(TGF)-α/β.

Angiogenic inhibitors: As used herein, “angiogenic inhibitors” refers tophysiological regulators that inhibit biosynthesis of vascularizationprocess. These regulatory compounds include, but not limited toangiostatin, thrombospondin-1 and interferon-α/β, platelet factorfactor-4, 16 kDa N-terminal fragments of prolactin, and endostatin.

Angiogenin: As used herein, “angiogenin” or “AGN” refers to anangiogenic-stimulating factor, which is also 14-kDa heparin-bindingprotein that occurs in most cells, also present in various biologicalfluids such as plasma and milk.

Phospholipid: As used herein, “phospholipids” refers to phosphated fattyacids, including but not limited to phosphatidyl glycerol, phosphatidylinositol, phosphatidyl serine, phosphatidyl choline, phosphatidylethanolamine, as well as phosphatidic acids, ceramides, cerebrosides,sphingomyelins and cardiolipins.

Antioxidant: As used herein, “antioxidant” refers to synthetic ornatural substances that prevent or delay the oxidative deterioration ofa compound. Exemplary antioxidants include tocopherols, flavonoids,catechins, superoxide dismutase (SOD), lecithin, gamma oryzanol;vitamins, such as vitamins A, C (ascorbic acid) and E and beta-carotene;natural components such as camosol, carnosic acid and rosmanol found inrosemary and hawthorn extract, proanthocyanidins (PAC) such as thosefound in grapeseed or pycnogenol found in maritime pine bark extract.

Catechin: As used herein, “catechin” refers to polyphenolic compoundsfound in many plants, green tea in particular, that could protect thebody from several diseases. These compounds include but not limited toepi-gallo catechin gallate (EGCG), epi-gallo catechin (EGC) andepi-catechin (EC).

Probiotic: As used herein, “probiotic” refers to nutritional supplementsof beneficial intestinal bacteria intended to re-colonize the intestinesto promote digestive health. A probiotic is also described as apreparation or a product containing viable, defined microorganisms withor without other substances in sufficient numbers, which improve oralter the microflora or their properties (by implantation orcolonization) in a compartment of the host and thereby exert beneficialhealth effects in the host. The commonly used probiotic microorganismsinclude but not limited to bacterial genus Lactobacillus, Lactococcus,and Bifidobacteria.

Effective amount: As used herein, “effective amount” refers to describeconcentrations or amounts of compounds according to the presentinvention which may be used to produce a favorable result, whether thatresult relates to a composition's therapeutic or physiological effect incompositions according to the present invention.

Daily Value: As used herein, “Daily Value” or “% DV” refers to describea term on food labels based on the RDA (Recommended Dietary Allowance)designed to help consumers use food label information to plan a healthydiet. The Daily Value serves as a basis for declaring on the label thepercent of the DV for each nutrient that a serving of the food provides.

Oral administration: As used herein, “oral administration” refers to anyform of delivery of an agent or composition thereof to a subject whereinthe agent or composition is placed in the mouth of the subject, whetheror not the agent or composition is swallowed. Thus, ‘oraladministration’ includes buccal and sublingual as well as esophagealadministration. Absorption of the agent can occur in any part or partsof the gastrointestinal tract including the mouth, esophagus, stomach,duodenum, ileum and colon.

Plant antioxidants: As used herein, “plant antioxidant” has its usualand customary meaning and includes carotenoids such as lycopene andlutein.

Embodiments of the invention provide physiologically deliverable,compositions comprising effective amounts of CoQ-10. More preferably,the CoQ-10 compositions of the preferred embodiments include LF and/orAGN, and optionally one or more bio-active agents. In a most preferredembodiment, composition include CoQ-10, angiogenin and LF. Compositionsof the invention also may include others components, such as oils, andother carriers. In preferred embodiments, delivery of the CoQ-10compositions is by the oral route;

In the present invention, the amount of CoQ-10 that is included in amixed composition depends upon the form of LF and may range from about0.1% to 90% by weight, preferably about 5% to 50% by weight, and mostpreferably about 10% to 20% by weight.

In an embodiment of the present invention, suitable CoQ-10 is availablefrom a variety of commercial sources (Alchem International from India,Daewoog from Korea, Xi'an Yier Hi-Tech Industry and Terio Corporationfrom China, and Kaneka Corporation from Japan). These suppliers mayproduce CoQ-10 by different methods, including but not limited tocontrolled microbial fermentation, direct chemical extraction fromanimal tissue (eg. beef heart) or higher plants (eg. tobacco, followedby synthetic alteration of the side chain). Some differences may existbetween CoQ-10 prepared from systems comprising prokaryotic andeukaryotic biosynthesis. CoQ-10 from fermentation technology may use anarray of microbial systems including bacteria (eg. Gluconobactersuboxydans, Agrobacterium tumefaciens, Sporidiobolus ruineniae), yeast(eg. Schizosaccharomyces pombe), or fungi (eg. Rhodotorula minuta,Leucosporidium scotti, Aspergillus clavatus, Bulleromyces albus).

In the present invention, the effective amounts of LF in a mixedcomposition may range from about 0.1% to 90% by weight, preferably about1% to 25% by weight, and most preferably about 5% to 10% by weight.

Suitable lactoferrin is available from various commercial sources(N-terminus or Glanbia from USA, Tatua or Fonterra from New Zealand, MGNutritionals from Australia, Morinaga Milk Company from Japan, DMVInternational from the Netherlands). Suitable lactoferrin can beisolated from dairy sources including colostrum, milk, and whey; milkserum from humans, cows, buffalos, horses, sheep, pigs or camels.Additionally the ultra-cleansed lactoferrin preparation can be purifiedfrom recombinant sources and genetically-modified organisms (GMOs).

In an embodiment of the present invention, in a mixed composition, LFmay be partially chelated (covalently bound) to a metal ion includingbut not limited to iron, zinc, copper, manganese, chromium, aluminum andgallium; preferably bound to iron, zinc and copper, most preferablybound to copper.

In another embodiment of the present invention, LF-copper metalcomplexes are prepared by adding LF protein with citrated copper sulfatesolution containing excess of citric acid (pH 2.5; 60 mol citrate: 1 molcopper). After incubation for 10 min, pH is raised to 7.0 with 0.1MNaOH. Sodium bicarbonate is added in excess (2 mol bicarbonate: 1 molcopper) and any unbound copper is removed (if necessary) by gelfiltration.

In another embodiment of the present invention, LF may be formed into acomplex with CoQ-10 by physical and/or chemical interactions. LF andCoQ-10 may be complexed together directly or they may be complexed bymeans of an appropriate bifunctional reagent. The LF:CoQ-10 complex maybe a covalent or non-covalent complex. A non-covalent complex may beformed by means of electrostatic interactions which may be enhanced byinclusion of appropriate buffers and/or salts. In one preferredembodiment, Cu-LF is complexed with either CoQ-10 or AGN.

In the present invention, the effective amounts of AGN in a mixedcomposition may range from about 0.1% to 90% by weight, preferably about0.5% to 25% by weight, and most preferably about 1% to 10% by weight.

In yet another embodiment of the present invention, LF can be mixed withAGN, directly during the chemical extraction-isolation process, eitherby co-eluting both protein fractions under similar chromatographicconditions, or by combining both the fractions at pre-determined ratiosafter the isolation process. In a preferred embodiment, LF and AGN areco-isolated from milk by a purification scheme that provides a fractionenriched in both LF and AGN. In a most preferred embodiment, LF and AGNare isolated from milk separately, but then recombined at the desiredratio before a lyophillization step. Lyophillization may be carried outby any means known in the art, preferably by freeze-drying orspray-drying. Once the lyophillized powder containing LF and AGN isobtained, the powder can be milled to provide a LF:AGN premix powder atthe desired ratio of LF and AGN. Alternatively, LF and AGN can beseparately isolated and dried to a purified powder. The purified LF andAGN powders can then be mixed together to provide a LF:AGN premix of thedesired ratio.

In the present invention, the ratios of LF:AGN premix may range between100:1 to 1:100, preferably 10:1 to 1:10, most preferably 6:1 to 3:1,respectively.

Suitable AGN can be isolated from dairy sources including colostrum,milk, whey and milk serum from humans, cows, buffalos, horses, sheep,pigs or camels. Additionally, AGN also can be purified from otherbiological fluids from animals (eg. blood), recombinant sources andgenetically-modified organisms (GMOs).

In an embodiment of the present invention, AGN may be combined withcopper and zinc, preferably copper. Direct interaction of copper andzinc could increase AGN binding to endothelial cells. Since copper is aknown modulator of angiogenesis in vivo, it may be engaged in theregulation of AGN activity. [Soncin F, et al. Interaction of humanangiogenin with copper modulates angiogenin binding to endothelialcells. Biochem Biophys Res Commun 236:604-610, 1997].

In another embodiment of the present invention, AGN may be formed into acomplex with LF by physical and/or chemical interactions. AGN and LF maybe complexed together directly or they may be complexed by means of anappropriate bifunctional reagent. A non-covalent complex may be formedby means of electrostatic interactions which may be enhanced byinclusion of appropriate buffers and/or salts.

In yet another embodiment of the present invention, AGN may be formedinto a complex with CoQ-10 by physical and/or chemical interactions. AGNand CoQ-10 may be complexed together directly or they may be complexedby means of an appropriate bifunctional reagent. A non-covalent complexmay be formed by means of electrostatic interactions which may beenhanced by inclusion of appropriate buffers and/or salts. AGN containsa signal peptide, called the nuclear localization sequence (NLS) in itsamino acid sequence that mediates its import into the nucleus. NLS islocated in the N-terminal region of human AGN comprised of the aminoacid residues from 31-35, i.e. RRRGL. Therefore, when linked tonon-nuclear molecules the NLS signal peptide of AGN is able to transportthe attached compounds into the nucleus. [Moroianu J, Riordan J F.Identification of the nuclear targeting signal of human angiogenin.Biochem Biophys Res Comm 203:1765-1772, 1994].

CoQ-10 formulation may include optionally one or more bio-active agents,an acceptable carrier, such as oil, or other suspending agent;flavoring, coloring agents or combinations thereof.

Optional bio-active agents that can be incorporated into the CoQ-10compositions of the present invention include, without limitation,L-carnitine, phospholipids, antioxidants, vitamins, amino acids,proteins, essential minerals and derivatives thereof or combinationsthereof.

L-carnitine is recognized in the art, a bio-activity that facilitatestransport of materials through the mitochondrial membrane. L-carnitineis an essential co-factor in fatty acid metabolism that helps move fattyacids to the mitochondria from the cytoplasm. This is an importantprocess required for the cellular uptake of CoQ-10. Carnitine is oftenused for heart conditions and it may be useful to treat angina or chestpain. Carnitine is also useful in the treatment of CHF and intermittentclaudication. Although carnitine does not increase blood flow, it isbelieved that it helps muscles to perform better under difficult painfulcircumstances, such as those associated with claudication.

In some embodiments of the present invention, L-carnitine is included incombination with CoQ-10. Suitable ratios of L-carnitine and CoQ-10 areknown in the art and include those described in U.S. Pat. No. 4,599,232,the teachings of which are incorporated herein in their entirety. Theactions of carnitine and CoQ-10 are interrelated. In fact, carnitine,through beta-oxidation of fatty acids, is able to restore the energysupplies necessary for cell life, whereas CoQ-10 is able to restore theATP supplies necessary for the energetic metabolic processes of thecell.

In the present invention, the effective amounts of L-carnitine in amixed composition may range from about 0.1% to 75% by weight, preferablyabout 1% to 50% by weight, and most preferably about 5% to 25% byweight.

Phospholipids are fats that are essential to the healthy structure ofcell membranes, particularly, in the brain. Docosahexaenoic acid (DHA)is an essential fatty acid present in brain phospholipids. It workstogether with the cerebral bio-active molecules to achieve thecomposition of key phospholipids needed for optimal cell membranefunction. Additionally, DHA helps protect against damage that can killcells and cause the breakdown of the brain's cellular structure.

The formulations of the invention can further include variousphospholipids. Non-limiting examples include phosphatidyl glycerol,phosphatidyl inositol, phosphatidyl serine, phosphatidyl choline,phosphatidyl ethanolamine, as well as phosphatidic acids, ceramides,cerebrosides, sphingomyelins and cardiolipins.

In the present invention, the effective amounts of phospholipids in amixed composition may range from about 0.1% to 75% by weight, preferablyabout 1% to 50% by weight, and most preferably about 5% to 25% byweight.

The formulations of the invention can further include various bio-activeingredients to help promote the functionality of the CoQ-10, or serve asadditional nutrients to an individual's diet. Suitable additives caninclude vitamins and biologically-acceptable minerals. Non-limitingexamples of vitamins include vitamin A, B vitamins, vitamin C, vitaminD, vitamin E, vitamin K and folic acid. Non-limiting examples ofminerals include iron, calcium, magnesium, potassium, copper, chromium,zinc, molybdenum, iodine, boron, selenium, manganese, derivativesthereof or combinations thereof. These vitamins and minerals may be fromany source or combination of sources, without limitation. Non-limitingexemplary B vitamins include, without limitation, thiamine, niacinamide,pyridoxine, riboflavin, cyanocobalamin, biotin, pantothenic acid orcombinations thereof.

In the present invention, the effective amounts of vitamins and/orminerals may be incorporated in the compositions according to theirrespective ‘Percent Daily Values’. Vitamin(s), if present, are presentin the composition of the invention in an amount ranging from about 1%to 1000% DV. More particularly, the vitamin(s) is present in an amountranging from about 10% to 250% DV. Most specifically, the vitamin(s) ispresent in an amount ranging from about 25% to 100% DV. For example, Bvitamins are in usually incorporated in the range of about 50% to 1000%DV, i.e., from about 100% to 1000% DV of B12. Folic acid, for example,is generally incorporated in a range of about 25% to 250% DV, biotin isgenerally incorporated in a range of about 10% to about 200% DV and B6is incorporated in a range of about 100% to 500% DV.

Mineral(s), if present, are present in the composition of the inventionin an amount ranging from about 1% to about 200% DV. More particularly,the mineral(s) are present in the composition ranging from about 10% to100% DV.

Suitable carriers include but are not limited to, for example, fattyacids, esters and salts thereof, that can be derived from any source,including, without limitation, natural or synthetic oils, fats, waxes orcombinations thereof. Moreover, the fatty acids can be derived, withoutlimitation, from non-hydrogenated oils, partially hydrogenated oils,fully hydrogenated oils or combinations thereof. Non-limiting exemplarysources of fatty acids (their esters and salts) include seed oil, fishor marine oil, canola oil, vegetable oil, safflower oil, sunflower oil,nasturtium seed oil, mustard seed oil, olive oil, sesame oil, soybeanoil, corn oil, peanut oil, cottonseed oil, rice bran oil, palm oil,rapeseed oil, palm kernel oil, lupin oil, coconut oil, flaxseed oil,evening primrose oil, jojoba, tallow, beef tallow, butter, chicken fat,lard, dairy butter fat, butter or combinations thereof.

Specific non-limiting exemplary fish or marine oil sources includeshellfish oil, tuna oil, mackerel oil, salmon oil, menhaden, anchovy,herring, trout, sardines or combinations thereof. In particular, thesource of the fatty acids is fish or marine oil (DHA or EPA), soybeanoil or flaxseed oil. Alternatively or in combination with one of theabove identified carrier, beeswax can be used as a suitable carrier, aswell as suspending agents such as silica (silicon dioxide).

Another optional component of the inventive CoQ-10 blend compositions islecithin. Lecithin, which is conventionally used as a liposome-formingagent, is a phospholipid made up of polar heads pointing inward andnon-polar tails pointing outward. Liposome formation can be used touptake of the dual hydrophobic-hydrophilic components of the inventivecompositions provided herein. Liposomes such as lecithin can, therefore,improve the ‘absorption’ of CoQ-10 compositions of the invention ingastro-intestinal tract.

If present, the amount of lecithin that is included in a mixedcomposition of the invention ranges from about 0% to about 98% byweight, preferably about 10% to about 60% by weight, more preferablyabout 20% to about 50% by weight and most preferably about 30% byweight.

The formulations of the present invention can further include probioticlactic acid bacteria (LAB) in a viable cell preparation or a non-viablecell preparation in the form of a freeze-dried powder or an emulsion fordelivery with CoQ-10 formulations.

The probiotic organisms envisaged in accordance with this inventionincludes a physiologically effective dosage of at least one LAB strain,typically in the form of a freeze-dried powder or emulsion, selectedfrom a group consisting of but not limited to the strains of bacteria ofthe genus Lactobacillus including L. acidophilus, L. amylovorus, L.animalis, L. bavaricus, L. brevis, L. bulgaricus, L. casei spp casei, L.casei spp rhamnosus, L. crispatus, L. delbrueckii ssp lactis, L.eichmanni, L. fermentum, L. helveticus, L. jensenii, L. kefir, L.paracasei, L. pentosus L. plantarum, L. reuteri, L. salivarius, and L.sake; the genus Leuconostoc including Leu. cremoris and Leu. lactis; thegenus Bifidobacterium including B. adolescentis, B. animalis, B.bifidum, B. breve, B. infantis, B longum, and B. thermophilum; the genusPediococcus including Ped. acidilactici and Ped. pentosus; the genusPeptostreptococcus including Pep. assacharolyticus, and Pep. productus;the genus Propionibacterium including Pro. acidipropionici, Pro.freudenreichii, Pro. jensenii, and Pro. theonii; the genus Streptococcusincluding S. cremoris, S. faecium, S. lactis, S. raffinolactis, and S.thermophilus. The probiotic organisms are collectively known as “lacticacid bacteria”; or “LAB”.

The effective dosages of probiotic in a mixed composition range between10² to 10¹² colony forming units; preferably between 10⁵ to 10¹⁰ colonyforming units per serving. Wherein the non-viable counts of probiotic ina mixed composition range between 10² to 10¹² colony forming units;preferably between 10⁵ to 10¹⁰ colony forming units per serving.

Formulations/Compositions with “CoQ-10 Blend”

CoQ-10 blends can be formulated in a variety of dosage forms thatinclude, without limitation, chewable tablets, elixirs, liquids,solutions, suspensions, emulsions, capsules, soft gelatin capsules, hardgelatin capsules, caplets, lozenges, chewable lozenges, suppositories,creams, topicals, ingestibles, injectables, infusions, health bars,confections, animal feeds, cereals, cereal coatings, and combinationsthereof. The preparation of the above dosage forms are well known topersons of ordinary skill in the art.

Design of formulations/compositions dependent upon the specificapplications of CoQ-10. For systemic administration, CoQ-10 blends canbe formulated in aqueous solutions, preferably in physiologicallycompatible buffers. For trans-mucosal administration, diffusion agentsthat could cross the mucosal barrier to be used in the formulation. Suchagents are generally known in the art.

For oral administration, CoQ-10 blends can be combined with carrierssuitable for inclusion into tablets, pills, capsules, liquids, gels,syrups, slurries, and suspensions. In a preferred embodiment,administration is by soft gel capsule. Soft, sealed capsules may be madeof gelatin and a plasticizer, such as glycerol or sorbitol. Preferably,the gel material is a bovine gelatin, fish gelatin, lecithin, fattyacid(s), oil or wax. CoQ-10 and other ingredients are dissolved orsuspended in suitable liquids, including oils, paraffin oil or liquidpolyethylene glycols, optionally in combination with a stabilizer.Preferred oils include seed oil, fish or marine oil, canola oil,vegetable oil, safflower oil, sunflower oil, nasturtium seed oil,mustard seed oil, olive oil, sesame oil, soybean oil, corn oil, peanutoil, cottonseed oil, rice bran oil, palm oil, rapeseed oil, palm kerneloil, lupin oil, coconut oil, flaxseed oil, and evening primrose oil.

For administration by inhalation, CoQ-10 blends are delivered in theform of an aerosol spray with the use of a suitable propellant frompressurized packs or a nebulizer. CoQ-10 blends can also be formulatedfor parenteral administration, e.g., by bolus injection or continuousinfusion. Such formulations can be suspensions, solutions or emulsionsin oily or aqueous vehicles, and can contain agents to suspend,stabilize and/or disperse active ingredients. For application to theskin, CoQ-10 blends can be formulated into a suitable gel, magma, cream,ointment, or other carrier. For application to the eyes, the source ofCoQ-10 blends can be formulated in aqueous solutions, preferably inphysiologically compatible buffers.

Controlled-Release

In addition to the common dosage forms, the CoQ-10 blends of the presentinvention may also be administered by controlled release mechanism,delivery devices, or both, which are well known to those of ordinaryskill in the art, such as those described in U.S. Pat. Nos. 3,845,770;3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595;5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; and 5,733,566,the disclosures of which are hereby incorporated by reference. Thesepharmaceutical compositions can be used to provide slow orcontrolled-release of CoQ-10 blends using, for example,hydropropylmethyl cellulose in varying proportions to provide thedesired release effects, other polymer matrices, gels, permeablemembranes, osmotic systems, multi-layer coatings, microparticles,liposomes, microspheres, or the like, or a combination thereof.

The controlled-release of CoQ-10 blends may be stimulated by variousinducers, for example pH, temperature, enzymes, water, or otherphysiological conditions or compounds. The term “controlled-releasecomponent” in the context of the present invention is defined herein asa compound or compounds, including polymers, polymer matrices, gels,permeable membranes, liposomes, microspheres, or the like, or acombination thereof, that facilitates the controlled-release of CoQ-10in a defined formulation.

Advantages of controlled-release formulations may include: i) extendedactivity of the drug; ii) reduced dosage frequency; and iii) increasedpatient compliance. Controlled-release formulations of the invention aredesigned to release an amount of CoQ-10 that provides a desiredphysiological effect, followed by the gradual and continuous release ofother amounts of active ingredients to maintain this level of effectover an extended period of time. In order to maintain this constantlevel of effect in the body, CoQ-10 needs to be released at a rate thatwill replenish the amount of CoQ-10 being metabolized and excreted bythe body.

Methods of Administering CoQ-10 Formulations/Compositions

Formulations/compositions based on CoQ-10 blend of the present inventionand pharmaceutical formats thereof can be used to treat any number ofconditions. “Treat” as used herein refer to reduction in severity and/orfrequency of symptoms, elimination of symptoms and/or underlying cause,prevention of the occurrence of symptoms and/or their underlying cause,and improvement or remediation of damage that is associated with aparticular condition.

The compositions according to the invention can be administered in acircumstance in which increased CoQ-10 levels are desired. Diseasestates, disorders or conditions which may be treated include but are notlimited to cardiovascular conditions including but not limited tocoronary heart disease, irregular heartbeat, high blood pressure, andcertain blood circulation disorders; age-related degenerative diseases,periodontal disease, impaired memory, fatigue, immune system impairment,and the aging process. The amount of CoQ-10 to be administered dependsupon the degree of the effect desired. Those skilled in the art willderive appropriate dosages and schedules of administration to suit thespecific circumstances and needs of an individual.

Generally, the formulations as described herein are suitable foradministration as a daily dose. The dose may be administered once dailyor, if desired, in several, optionally equal, partial doses. Dosagedepends upon various factors including sex, age, weight and individualcondition. For some individuals, particularly those with specificconditions, higher doses or more frequent doses may be indicated.

EXAMPLES

Compositions containing CoQ-10, LF and AGN can be prepared either bymixing effective amounts of the all three active ingredients into aformula, as individual components; or by adding an effective dosage of apremix of two or all of the three active ingredients at specificpre-calculated ratios.

Example-1 CoQ-10/LF/AGN Premix Compositions

TABLE 1 CoQ-10:LF:AGN Premix 10:6:1 Ingredient 10:3:1 Premix 20:6:1Premix Premix CoQ-10 100 mg 60 mg 100 mg 60 mg 100 mg LF  30 mg 18 mg 30 mg 18 mg  60 mg AGN  10 mg  6 mg  5 mg  3 mg  10 mg Total Premix 140mg 84 mg 135 mg 81 mg 170 mg

Appropriate CoQ-10/LF/AGN premix can be incorporated into a specificformulation, at effective amounts as required. For instance, adding 250mg of CoQ-10/LF/AGN premix (10:3:1) to formulations amounts to 178.6 mgof CoQ-10, 53.6 mg of LF, and 17.8 mg of AGN.

Example-2 LF/AGN Premix Compositions

TABLE 2 LF:AGN Premix Ingredient 3:1 Premix 2:1 Premix 6:1 Premix LF 30mg 18 mg 30 mg 150 mg 60 mg AGN 10 mg  6 mg 15 mg  75 mg 10 mg TotalPremix 40 mg 24 mg 45 mg 225 mg 70 mg

Appropriate LF/AGN premix can be incorporated into a specificformulation, at effective amounts as required. For instance, adding 250mg of LF/AGN premix (6:1) to formulations amounts to 214.3 mg of LF, and35.7 mg of AGN.

Formulations for Cardiovascular Health

Example-3 Soft Gel or Soft Gelatin Capsules for Cardiovascular Health

For cardiovascular health, exemplary soft gel or soft gelatin capsulescan be prepared, without limitation, by dispersion of CoQ-10 blend in anappropriate vehicle to form a high viscosity mixture, by usingconventional methods well known in the art. Soft elastic gelatincapsules have a soft, globular gelatin shell, somewhat thicker than thatof hard gelatin capsules. In such soft gel formats, gelatin isplasticized by the addition of plasticizing agent, e.g., glycerin,sorbitol, or a similar polyol. The hardness of the capsule shell can bealtered with appropriate type of gelatin and the amounts of plasticizerand water. Soft gelatin shells may contain a preservative, such asmethyl- and propylparabens and sorbic acid, to prevent any fungalgrowth. CoQ-10 blend may be dissolved or suspended in a liquid vehicleor carrier, such as vegetable or mineral oils, glycols such aspolyethylene glycol and propylene glycol, triglycerides, surfactantssuch as polysorbates, or a combination thereof. Typically, the weight ofthe capsule may range between about 100 to 2500 milligrams; inparticular, weigh between about 500 and 2000 milligrams; and morespecifically, weigh between about 750 and 1500 milligrams.

TABLE 3 Ingredient Per Serving % DV CoQ-10 100 mg † Lactoferrin* 30 mg †Angiogenin* 10 mg † Acetyl L-carnitine 100 mg † Non-GE Soy Lecithin 15mg † Vitamin-B6 (from Pyridoxine HCl) 5 mg 250% Vitamin-E(d-Alpha-Tocopherol Acetate) 30 IU 100% Selenium (from SeleniumAspartate) 69 mcg 100% Copper (76.7% Copper Oxide) 2 mg 100% FlaxseedOil 300 mg † *LF and AGN can be incorporated as 40 mg (3:1) premixinstead of individual ingredients.Formulations for Sports Nutrition

The term “sports performance” as used herein, refers to the ability ofthe athlete's muscles to perform when participating in sportsactivities, including but not limited to, aerobic exercise, and bodybuilding. Enhanced sports performance, strength, speed and endurance aremeasured by an increase in muscular contraction strength, shortening ofmuscle reaction time between stimulation and contraction. Sportsperformance is intended to stimulate muscle tissue through contractionand extension of the muscle fibers. Each contraction and extension, whenperformed under stress, results in damage to the muscle tissue. Thedamaged tissue is repaired after the exercise, which leads to formationof additional muscle tissue resulting in muscle growth.

During exercise-related tissue recovery, muscle requires protein (thesource of amino acids), calories and other nutrients, includingvitamins, salts, minerals and phytochemicals. Previous inventions haveutilized specific application of certain amino acids (carnitine,glutamine, isoleucine, leucine, and valine) to exert net stimulatoryeffects on protein synthesis in skeletal muscle.

The purpose of sports nutrition is to build more muscle tissue fasterand to prevent injuries. A variety of products are marketed for thispurpose including protein powders, supplemented amino acids, hormones,pro-hormones, and hormone-like chemicals. Protein powders are the mostcommon form of dietary supplements in sports nutrition. Most athletessupplement their daily diet with extra protein in the form of powders orready-to-drink protein shakes. Protein is metabolized to its buildingblocks, the amino acids, which can be used by the body to synthesizenecessary cellular mass and anabolic hormones for synthesis of newmuscle tissue.

Incorporation of CoQ-10 blend of the present invention, with specificingredients provides several synergistic health benefits, includingproduction of an anabolic (body building) metabolic reaction when theproduct is consumed.

As used herein, “source of amino acid” means any peptide, polypeptide,protein or any complex of individual amino acids or individual aminoacid. Throughout the present specification, as part of the sportsperformance supplement of the invention, whey protein or a derivativethereof are identified as the preferred source of amino acids orprotein. A suitable protein could also be obtained from whey, milkpeptides and milk serum, casein and casein hydrolysates, albuminincluding chicken egg albumin, and soy, may be used as a source of aminoacids.

Sports performance supplement compositions may further comprise variousvitamins and antioxidants, including vitamin-A (β-carotene), B-complex(including thiamine, niacin, nicotinic acid, niacinamide, pantothenicacid, pyridoxine, cyanocobalamin, biotin and folic acid), vitamin-C(ascorbic acid), vitamin-D, and vitamin-E in amounts equal to orexceeding the recommended minimum daily requirements. Suitableantioxidants include phytophenols (eg. catechols from tea) andbioflavonoids (eg. anthocyanins from grapes).

Suitable salts include, but not limited to, alkali and alkaline earthmetal salts, for example sodium, potassium or calcium salts, whilesuitable minerals include, but not limited to, magnesium, chromium,selenium, or zinc.

The sports performance supplement compositions of the present inventionmay be provided in a variety of formats, including but not limited to,liquid form, powder form, or protein bar form. Powders are preferableand are prepared to be suitable for mixing with water or other liquids.The sports performance supplement compositions in powder or granularform may be provided in accordance with customary processing techniques,for example as spray dried powders, or the like.

Example-4 Protein Powders for Body Building (Increasing Lean Mass andStrength)

TABLE 4 Ingredient Per Serving % DV Coenzyme Q-10 120 mg †Lactoferrin-(tcr)* 180 mg † Angiogenin* 30 mg † Vitamin B1 (as ThiamineMono) 1.5 mg 100% Vitamin B2 (as Riboflavin) 1.7 mg 100% Vitamin B3 (asNiacinamide) 20 mg 100% Vitamin B5 (as Calcium Pantothenate) 10 mg 100%Vitamin B6 (as Pyridoxine HCl) 5 mg 250% Vitamin B12 (as Cyanocobalamin)15 mcg 250% Folic acid 400 mcg 100% Biotin 300 mcg 100% Vitamin-C(Calcium L-ascorbate) 120 mg 200% Vitamin-E (d-Alpha-Tocopherol Acetate)30 IU 100% L-Glutamine 5.0 g † Taurine 1.0 g † N-acetyl-creatine 5.0 g †N-acetyl-cysteine 0.5 g † L-Glycine 3.0 g † L-Leucine 1.0 g † L-Arginine100 mg † Acetyl L-carnitine 200 mg † Sodium (as citrate) 50 mg †Potassium (as citrate) 40 mg  1% Selenium (from Selenium Aspartate) 69mcg 100% Magnesium (Magnesium Oxide) 8 mg  2% Copper (76.7% CopperOxide) 2 mg 100% Chromium (19% Chromium Chloride) 120 mcg 100% Milkprotein Concentrate As required † *LF and AGN can be incorporated as 210mg (6:1) premix instead of individual ingredients.

According to one embodiment, the supplement compositions of the presentinvention are delivered in powder on a per one “scoop” basis. As usedherein, one “scoop” is approximately 28 g of supplement.

Example-5 Supplement for Exercise Recovery

The following formulation promotes tissue recovery after exercise whileproviding energy and preventing oxidation damage. Vascularizationimproves as body mass increases. This formulation is particularly usefulfor body builders including weight lifters, professional athletes anddancers, and particularly for increasing muscle mass. This formulationmay be prepared as a powder to be added to milk, water, yogurt or otherfood substance as a nutritional supplement.

TABLE 5 Ingredient Per Serving % DV CoQ-10 100 mg † Lactoferrin* 60 mg †Angiogenin* 20 mg † Non-GE Soy Lecithin 15 mg † Vitamin-B6 (fromPyridoxine HCl) 5 mg 250% Vitamin-E (d-Alpha-Tocopherol Acetate) 30 IU100% Selenium (from Selenium Aspartate) 69 mcg 100% Copper (76.7% CopperOxide) 2 mg 100% Protein powder (milk, egg, whey, or soy) 10-20 g †L-taurine 1 g † N-acetyl creatine 5 g † Dehydroepiandrosterone (DHEA) 50mg † Amino Acid blend 4 g † (glycine, leucine, arginine, taurine)Choline 200 mg † Inositol hexanicotinate 25 mg † *LF and AGN can beincorporated as 80 mg (3:1) premix instead of individual ingredients.

Nitric oxide (NO) is essential for muscle contraction and dilation ofblood vessels. This cellular function is vital for widening of bloodvessels to support an increased blood flow for greater oxygen andnutrient delivery. Body builders, in particular, need such increase inblood flow for maximum oxygen and nutrient delivery. Taurine plays animportant role in NO production, and is therefore, a useful supplementto maintain or increase NO production.

DHEA is an androgen (male sex hormone) produced in the adrenal glands,and is one of the main precursors of testosterone. DHEA levels candecline up to 90% with age, therefore, is often used to boost sexhormone levels, and used by athletes to boost testosterone levels.Studies have shown that supplementing 50-100 mg of DHEA per day helpincrease muscle mass and improve overall health condition.

The formulation can optionally contain human growth hormones (hGF) orhGF precursors and stimulators; testosterone or testosterone precursors(eg. androstenediol) and stimulators (extracts from Tribulus terristisor Avena sativa).

Example-6 Beverages for Cardio-Aerobic Performance

For cardio-aerobic performance, CoQ-10 blends suitable for use in thepresent invention include any beverage that forms an amount of foodresidue in the digestive tract or that forms an amount of residue whichdoes not impede or adversely affect a predetermined activity or theoutcome of such activity. Such beverages may include, but are notlimited to, drinks containing natural, e.g., fruit or vegetable, and/orartificial ingredients such as iced tea or coffee, coffee, herbal teas,fruit juices, sports-drinks, sodas, soft drinks and the like. Suitablebeverages may include blends of various ingredients compounded in drypowder form or effervescent tablets that readily dissolve in a fluid,such as water. Such beverages may also comprise a blend of organicingredients, such as whole herbs, or may include vitamin or herbalenhanced waters in various flavors.

The CoQ-10 formulation suitable for beverage use in the presentinvention includes, but is not limited to, any flavored drink comprisingsugar, malic acid, aspartame, sodium citrate, natural and artificialflavors/colors and phenylalanine.

TABLE 6 Ingredient Per Serving % DV Coenzyme Q-10 50 mg †Lactoferrin-(tcr)* 30 mg † Angiogenin* 5 mg † Pycnogenol (extract fromPinus pinaster) 45 mg † L-arginine 100 mg † L-lysine 200 mg † Vitamin-C(as Calcium L-Ascorbate) 120 mg 200% Selenium (from Selenium Aspartate)69 mcg 100% *LF and AGN can be incorporated as 35 mg (6:1) premixinstead of individual ingredients.

In one alternative embodiment of the present invention, an appropriateserving of a drink may also contain B-complex vitamins and/or mineralssuch that it provides appropriate nutrition.

Lactoferrin-(tcr) may be prepared as described in U.S. Application No.2005/0197495, which is incorporated herein by reference. Basically, a 1%(v/v) polysorbate-80 solution, a 0.5% solution of vitamin C (ascalcium-L-ascorbate) with 10 mM sodium bicarbonate and 95% (w/v)turmeric root extract (0.1% curcumin) were used in the TCR process assurfactant, antioxidant and polyphenolic tiers, respectively. LF powderwas dissolved in 100 mL of polysorbate-80 solution with gentle stirringat room temperature for 2 h. Ten minutes after adding 10 g LF topolysorbate-80 (100 mL) the solution was mixed with calcium-L-ascorbate(0.5 g) and 10 mM sodium bicarbonate and stirred at room temperature for2 h. Ten minutes later, a polyphenolic phase was included with theaddition of 1% curcumin to the solution with continuous stirring at roomtemperature for 2 h. By this process, the aerobic plate count ismarkedly reduced by more than 99.9% and the endotoxin activity isgreatly diminished almost to undetectable level.

Example-7 Meal Replacement Health Bars to Reduce or Prevent VascularPlaque

For prevention of vascular plaque formation, CoQ-10 blends suitable foruse in the present invention can be designed as “health bars” toapproximate a meal-equivalent. Such health bars may include rolled oatsand bran mixed with the soy protein to form the common bar “oat-soy”material, to which the ingredients of CoQ-10 formulation will be admixedwith appetite-stimulants that may include high-fat and sour taste (eg:oil and vinegar); appetite-depressants that may include low-fat, fiber,and bitter taste (eg: starch, edible gum, and quinine). Alternative oradditional ingredients may be carbohydrates derived from other grains,fruits, and vegetables; with proteins derived from nuts, beans, eggs,cheese, meat, fish, and fowl. Soluble and insoluble fiber sourcesinclude apples, potatoes, and gum plants. Vitamins, minerals, and otheradditives.

TABLE 7 Ingredient Per Serving % DV Coenzyme Q-10 30 mg † Lactoferrin*30 mg † Angiogenin*  5 mg † Pantethine 50 mg † Lycopene 1.0 mg  † Lutein0.5 mg  † L-carnitine (fumarate) 50 mg † Vitamin-B6 (from PyridoxineHCl)  2 mg 100% Vitamin-C (from Calcium Ascorbate) 60 mg 100% Lecithin100 mg  † Chitosan 100 mg  † Red yeast rice 200 mg  † *LF and AGN can beincorporated as 35 mg (6:1) premix instead of individual ingredients.

Health bar can be prepared, without limitation, by mixing CoQ-10 blendwith all the ingredients of the formulation with excipients (e.g.,binders, fillers, flavors, colors, etc.) to a plastic mass consistency.The mass is then either extended or molded to form “rectangular bar”shapes that are then dried or allowed to solidify to form the finalproduct.

Formulations for Healthy Management of Female Hormone Transitions (HT)

Hormones are vital chemical substances in our body. Women, inparticular, undergo three major hormonal transitions (HT) during theirlife-time, namely: “HT-1”, the reproductive (menstruation) phase;“HT-2”, the peri-menopause phase; and “HT-3”, the post-menopause phase.The four major hormones, i.e. estrogen, progesterone, folliclestimulating hormone and luteinizing hormone, are involved with menstrualcycle and reproduction. In women, estrogen circulates in thebloodstream, binds to estrogen receptors to influence the functions ofbrain, bone, liver, heart and other tissues. Estrogen controls growth ofthe uterine lining during the first part of the menstrual cycle, causeschanges in the breasts during adolescence and pregnancy, and alsoregulates various metabolic processes, including bone growth andcholesterol levels.

LF is the body's own “natural regulator” of hormones and an activecomponent of the vaginal secretions and uterine luminal fluid. LF occursin the uterine epithelia at varying levels and fluctuates with the riseand fall of estrogen during the estrous cycle. LF is associated withestrogen; high levels enhance estrogen activity and low levels suppressit. [Zhang Z, Teng C T. Estrogen receptor-related receptor 1 interactswith coactivator and constitutively activates the estrogen responseelements of the human lactoferrin gene. J Biol Chem 275:20837-20846,2000].

Any depletion, deficiency or dysfunction of LF could put women throughpainful symptoms and predispose several health risks such asosteoporosis, coronary heart disease, and vaginal infections. Researchstudies have shown that LF supplementation could provide a naturalbalance during the hormonal transitions. Incorporation of CoQ-10 and AGNto the LF-based female hormonal transition formulations could provideseveral synergistic health benefits, including alleviation of manypainful symptoms. The following CoQ-10 blends are non-limiting examplesfor health management of all three phases of female HT.

Example-8 CoQ-10/AGN Containing LF-Based Formula for Female HT-1

The formulation described herein, could be beneficial, particularly forwomen undergoing HT-1 phase on a daily and monthly basis, during theirchild-bearing years. Women may encounter a recurrent and cyclical set ofphysical and behavioral symptoms that occur 7-14 days before themenstrual cycle. The symptoms may be troublesome enough to interferewith several aspects of a regular life, collectively referred to as“premenstrual syndrome (PMS)”.

TABLE 8 Ingredient Per Serving % DV Lactoferrin* 90 mg † CoQ-10 30 mg †Angiogenin* 10 mg † Borage Oil (>20% Gamma-Linolenic Acid) 300 mg †Evening Primrose oil 150 mg † Chaste Tree Extract 4:1 (Vitexagnus-castus) 20 mg † Vitamin-B1 (from Thiamine Mono) 1.5 mg 100%Vitamin-B2 (from Riboflavin) 1.7 mg 100% Vitamin-B3 (from Niacinamide)20 mg 100% Vitamin-B5 (from Calcium D-Pantothenate) 10 mg 100%Vitamin-B6 (from Pyridoxine HCl) 10 mg 500% Vitamin-B12 (fromCyanocobalamin) 6 mcg 100% Folic acid 200 mcg 50% Biotin 150 mcg 50%Calcium (from Calcium Citrate) 50 mg 10% Magnesium (from MagnesiumOxide) 20 mg 10% Chromium (19% Chromium Chloride) 30 mcg 25% SodiumBicarbonate USP 10 mg † Citric acid 20 mg † *LF and AGN can beincorporated as 100 mg (9:1) premix instead of individual ingredients.

An effective dosage of the formulations, as exemplified above, can beadministered in the form of a soft-gel or a two-piece capsule. Asuitable two-piece capsule that can hold liquid without any leakage canbe prepared by using proper sealant or by converting the liquid into aform which is either solid or semi-solid at room temperature.

Example-9 CoQ-10/AGN Containing LF Compositions for Female HT-2(AM-Formula)

The formulation described herein, is beneficial for women undergoingHT-2, a phase in every woman's life with the continued absence of amenstrual cycle, leads to menopause. A woman's body adjusts to thedeclining estrogen during the HT-2 phase by balancing the progesteronelevels. Several physical and emotional changes are associated withfluctuating estrogen levels during the hormonal transition to menopause;a process medically termed as “perimenopause”, which typically lastsabout 5 years for most women.

The following “AM formula” is intended to relieve day-time symptomsincluding, mood changes, irritability, difficulty with memory andattention span, vaginal dryness, painful intercourse, dry eye syndrome,urinary leakage, skin and hair changes.

TABLE 9 Ingredient Per Serving % DV Lactoferrin* 45 mg † CoQ-10 30 mg †Angiogenin* 5 mg † Vitamin-B6 (from Pyridoxine HCl) 4 mg 200% Vitamin-E(d-alpha-Tocopherol Acetate) 30 IU 100% Vitamin-C (from CalciumAscorbate) 60 mg 100% Selenium (from Selenium Aspartate) 40 mcg  58%Calcium (from Calcium Ascorbate, Citrate) 50 mg  10% Magnesium (fromMagnesium Oxide) 5 mg  2.5% Potassium (from Potassium Chloride) 20 mg 0.5% Soy Protein Isolate 50 mg † Black Cohosh 30 mg † Red Clover 4:1Extract 20 mg † Soy Lecithin 15 mg † Sodium Bicarbonate USP 10 mg † *LFand AGN can be incorporated as 100 mg (9:1) premix instead of individualingredients.

Example-10 CoQ-10/AGN Containing LF Compositions for Female HT-2(PM-Formula)

The “PM formula” described herein, is intended to relieve night-timesymptoms including hot flashes, night sweats, and insomnia.

TABLE 10 Ingredient Per Serving % DV Lactoferrin* 45 mg † CoQ-10 30 mg †Angiogenin* 5 mg † Vitamin-B5 (as Calcium D-Pantothenate) 20 mg 200%Vitamin-E (as d-alpha-Tocopheryl Acetate) 30 IU 100% Vitamin-C (fromCalcium Ascorbate) 60 mg 100% Selenium (from Selenium Aspartate) 40 mcg 58% Calcium (from Calcium Ascorbate, Citrate) 50 mg  10% Magnesium(from Magnesium Oxide) 5 mg  2.5% Potassium (from Potassium Chloride) 20mg  0.5% Gamma-oryzanol 20 mg † L-Theanine 30 mg † Valerian root 50 mg †Soy Lecithin 15 mg † Sodium bicarbonate USP 10 mg † *LF and AGN can beincorporated as 50 mg (9:1) premix instead of individual ingredients.

An effective amount of the AM and PM formulations, as exemplified above,can be administered in the form of a tablet or a two-piece capsule.Tablets can be prepared with pharmaceutically acceptable excipientsincluding fructose-DC, magnesium stearate, stearic acid, CanTab(tableting dextrose, Penford Food Ingredients, Englewood, Colo.),natural flavor and color (if necessary) were blended with theingredients from Table 10. Each of the above ingredients was placed, inpowdered form, into a commercial blender, mixed and, if necessary,passed through a mesh screen to remove aggregates. After 20 minutes ofthorough mixing, the composition is cold pressed in a tablet press setat a appropriate pressure and manufacturing methods commonly practicedin the art of manufacturing dietary supplements.

Example-11 CoQ-10/AGN Containing LF Compositions for Female HT-3

The formulation described herein, is beneficial for women undergoingHT-3, which normally occupies one-third of a woman's life, leads to“post menopause” and the total cessation of menstrual cycles. In time,hot flashes may seem milder or less frequent, emotional swings andenergy levels may become more stable, and most of the symptoms ofmenopause have faded. The HT-3 phase differs from the HT-1 and HT-2phases in the way that the sex hormones are biosynthesized. In women,sex hormones play a critical role in maintaining healthy bones, heartand blood vessels. The deficiency of sex hormones in post-menopauseincreases the risk of cardiovascular disease, osteoporosis, dryness ofthe vaginal walls, changes in the urinary tract and weight gain.

TABLE 11 Ingredient Per Serving % DV Lactoferrin* 90 mg † CoQ-10 30 mg †Angiogenin* 10 mg † Flaxseed Oil (>20% alpha-Linolenic Acid) 300 mg †Vitamin-D 200 IU 50% S-Adenosylmethionine (SAM-e) 200 mg † Calcium (fromCitrate) 50 mg 10% Magnesium (from Oxide) 20 mg  5% Chromium (19%chromium chloride) 30 mcg 25% Sodium Bicarbonate USP 10 mg † Citric acid20 mg † *LF and AGN can be incorporated as 100 mg (9:1) premix insteadof individual ingredients.

An effective dosage of the formulations, as exemplified above in Table11, can be administered in the form of a soft-gel or a two-piececapsule. A suitable two-piece capsule that can hold liquid without anyleakage can be prepared by using proper sealant or by converting theliquid into a form which is either solid or semi-solid at roomtemperature.

Formulations for Management of Vaginal Health

Example 12

The preparation of vaginal suppository compositions includes well knowntechniques of rolling (hand shaping), molding (fusion) and coldcompression. Suppositories are usually globular or oviform and weighabout 5 grams. Reference is made to Remington's Pharmaceutical Sciences,18th Edition, Chapter 87, pages 1609-13 (1990), the disclosure of whichis expressly incorporated herein by reference.

Preparation of a vaginal suppository containing the CoQ-10 blend can beprepared in accordance with well known techniques in the art. In atypical suppository formulation, the active agents are combined with anappropriate pharmaceutically acceptable suppository base such as cocoabutter, esterified fatty acids, glycerinated gelatin, and variouswater-soluble or dispersible bases like polyethylene glycols andpolyoxyethylene sorbitan fatty acid esters. Various additives,enhancers, or surfactants may be incorporated. Such suppositories willgenerally be constructed of a mixture of substances that are solid atroom temperature but melt at body temperature. The substances commonlyused to create such vehicles include, but are not limited to, theobromaoil, glycerinated gelatin, hydrogenated vegetable oils, mixtures ofpolyethylene glycols of various molecular weighty and fatty acid estersof polyethylene glycol.

The vaginal suppository may include a water soluble base to lowersurface tension for rapid dispersion of actives. A water-soluble basealso decreases the risk of secondary infection. Exemplary water solublebases include, but are not limited to, corn starch, aloe and cocoabutter.

The vaginal suppository compositions of the present invention may alsoinclude propylene glycol, which acts as a surfactant to assist inpenetration, contact, and absorption of the active ingredients.Propylene glycol also serves as a preservative and an antimicrobialagent.

Compositions of the vaginal suppository of the present invention mayalso include a non-ionic surfactant such as polysorbate to promotebetter surface contact of the ingredients with the vaginal mucosa byfurther reducing the surface tension.

Compositions of the vaginal suppository of the present invention mayalso be formulated in combination with other drugs, such as spermicides,antibiotics (antibacterials, antifungals such as fluconazole, antiviralsand antiparasitics) and anti-inflammatory agents, thereby furtherbroadening the composition's medical applications.

Compositions of the vaginal suppository of the present invention mayalso be pH balanced by the addition of a base including, but not limitedto, triethanolamine, sodium hydroxide and sodium bicarbonate to adjustthe pH to a level compatible with the tissue being treated. In thenormal vagina, the pH is in range of about 3.8 to 4.4. A humectant mayalso be included in the composition of the present invention, such asglycerin, to soothe the area being treated, for example, as a cleansingsolution.

Compositions of the present invention may contain a topical anestheticincluding, but not limited to, lidocaine hydrochloride and topicalsteroids, including but not limited to, corticosteroids, to providerelief from pain or itching during the treatment.

As will be understood by those skilled in the art, the regimen fortreating vaginal infection will depend on the severity of the infectionand the form of the composition. By way of a non-limiting example, wherethe composition is in the form of a cream, the cream is topicallyapplied to the affected area. Where the composition is in the form of asuppository, it is inserted into the vagina, in a non-limiting example,once or twice daily for 7 days.

Terms used herein are to be given their usual meaning in the art unlessotherwise stated. The term “vaginal infection” means any vaginalinfection of, bacterial, fungal or parasitic origin. Examples of some ofthe microorganisms which cause such infections include, but are notlimited to, microorganisms of the genus Candida, particularly C.albicans, C. tropicalis and C. glabrata, Gardneralla vaginalis, variousmixed anaerobic bacteria and Peptostreptococcus bacteria.

One vaginal suppository composition including CoQ-10 blend wasformulated as described below. In a non-limiting exemplary embodiment ofthe present invention, the CoQ-10/LF/AGN (2:10:1) premix formulation(150 mg) can be combined with hydrogen peroxide-producing Lactobacilluscrispatus (109 CFU/dose) together with an active lactoperoxidase systemcomprised of either Mixture (A) containing lactoperoxidase (1000 IU),urate oxidase (5000 IU), urate (500 mg) and potassium thiocyante (5 mg);or Mixture (B) containing lactoperoxidase (2000 IU), sodium thiocyanate(10 mg) and benzylalkonium chloride (10 μg). Finally, DMSO (0.1% finalconcentration) was incorporated to promote rapid tissue penetration.

Treatment of the vaginal infection may vary depending on the severity ofthe infection and appropriate treatment regimen known to those medicalpractitioners, particularly gynecologists. An exemplary, non-limitingtreatment regimen may involve insertion of a CoQ-10/LF/AGN (2:10:1premix)-containing suppository into the vagina twice daily for 7 days.

Douche solutions containing CoQ-10/LF/AGN (2:10:1 premix) can beprepared with other optional ingredients including, but not limited to,antimicrobial agents, anaesthetics or antipruitics (such as phenol ormenthol), astringents, surface active agents, propylene glycol, glycerinUSP and Polysorbate 20 (Liposorb L20). The solution may be initiallyformed as a concentrated liquid, dissolvable powder or tablet. When useis desired, water may be added, preferably warm in temperature toproduce a solution of desired concentration.

Formulations for Bone Health

LF is vital for bone growth and repair; boosts growth and activity ofosteoblasts (cells responsible for building bone); reduces, up to50-70%, the rate at which these cells die, and decreases the formationof osteoclasts (cells responsible for breaking down bone), thereby helpsto prevent or reverse osteoporosis. LF could also increase themultiplication of chondrocytes, the cells that build cartilage.Biosynthesized in the bone marrow, LF can modulate inflammatoryresponses by scavenging toxic “free” iron. This mechanism is importantat the sites of inflammation, such as in the rheumatoid joint. LF canbind “free” iron in the synovial fluid and reduce joint inflammationduring arthritis. Orally administered LF has preventive and therapeuticeffects in the treatment of rheumatoid arthritis. [Cornish J, et al.Lactoferrin is a potent regulator of bone cell activity and increasesbone formation in vitro. Endocrinol 145:4366-4374, 2004].

The combination of CoQ-10 blend with LF-based bone health formulationsprovides several benefits including energy for angiogenesis duringformation of bone mass.

Example-13 CoQ-10/AGN Containing LF-Based Bone Health Formulations

TABLE 12 Ingredient Actives % DV CoQ-10 30 mg † Lactoferrin (90%)* 90 mg† Angiogenin* 10 mg † Vitamin-D3 (as Cholecalciferol) 200 IU 50% Folicacid 100 mcg 25% Chondroitin Sulfate (from Chondroitin Sulfate 25 mg †Sodium) Glucosamine Sulfate (from Glucosamine Sulfate 75 mg † Potassium)Methylsulfonylmethane (MSM) 50 mg † Turmeric root extract 25 mg †Calcium (from Calcium Citrate) 50 mg  5% Sodium bicarbonate USP 30 mg †Yucca Schidegera Root Extract 10 mg † *LF and AGN can be incorporated as100 mg (9:1) premix instead of individual ingredients.

Other optional active ingredients suitable for the above bone healthformulations include but not limited to, S-adenosylmethionine (SAM-e),cerasomal-cis-9-cetylmyristoleate (CMO), and dimethylglycine (DMG).

Formulations for Oral Health-Care

Example-14 CoQ-10 Containing Mouthwash Formulations

A mouthwash base can be prepared by combining cetylpyridinium chloride(1 g), citric acid USP (1 g) and sweetener (q.s), dissolving in 100 mLdeionized water and mixing with 100 mL alcohol USP. Flavor oils(peppermint, eucalyptus and clove oils; 1.5 mL) were mixed withpolyoxyethylene, and sorbitan monostearate; this blend was slowly addedto the hydroalcoholic solution while stirring. A 70% sorbitol solution(200 g) was added and the volume made up to 1000 mL with deionizedwater. In one embodiment of the present invention, the CoQ-10/LF/AGN(2:10:1 premix) formulation and mouthwash base were mixed to homogeneityat 1:10 ratios. A formulation for a tooth powder is shown in Table 13.

TABLE 13 Ingredient % w/w range % DV CoQ-10 0.1-5.0% †Lactoferrin-(tcr)* 0.1-5.0% † Angiogenin* 0.01-1.0%  † Dextrose/Fructose(or polydextrose) 10.0-90.0% † xylitol  0.1-10.0% † Potassium sorbate0.01-1.0%  † Sodium benzoate 0.01-1.0%  † Zinc gluconate 0.001-0.1%  †*LF and AGN can be incorporated as (6:1) premix instead of individualingredients.Formulations for Wound-Care and Skin-Care

CoQ-10 formulations suitable for topical use on the skin can be in theform of an ointment, cream, lotion, paste, oil or spray. Carrierssuitable for such use include petrolatum, lanolin, polyethylene glycols(PEG), alcohols and combinations of these substances. Typically, the“active ingredient” in such products is in a concentration of about 0.1%to 15% by weight of the composition, for example from about 0.5% to 2%.The methods for preparing such topically applied formulations are wellknown in the art.

CoQ-10 formulations suitable for trans-dermal administration can be inthe form of single plasters which are suitable for long-term closecontact with the skin. Such plasters contains an effective quantity ofactive ingredients mixed in aqueous buffered solutions that readilydissolve and/or disperse in an adhesive polymer. A suitableconcentration of CoQ-10 blend is about 1% to 35%, preferably about 3% to15%. The methods for making trans-dermal patches are well known in theart. The term “effective amount” refers to a dosage efficient to treat aparticular infection and is determined by a person of skill in the art,such as a medical practitioner.

The term skin condition can refer to any state that results frombacterial, parasitic, fungal, insecticidal and actinomycotic infection;which also includes keratinization disorders. Non-limiting examples ofmicroorganisms which can cause such infections include Candidiaalbicans, microorganisms of the genera Trichophyton, Epidermophyton andMicrosporum, parasites such as Sarcoptes scabieii, Streptotrichosis,various dermatophytes, various types of ectoparasites and insects, forexample, fleas, lice and mites.

Example-15 Wound Care Formulation

A wound-care formula based on the CoQ-10/LF/AGN (2:20:1 premix) blendcan be applied repeatedly from the time when wound first occurs.Preferably, the CoQ-10 formula can be applied about every time when thewound dressing is changed. The CoQ-10 formula can also be applied aboutevery other day; more preferably, every day.

Numerous administration vehicles and delivery methods will be apparentto those of ordinary skill in the art including, without limitation,slow-release systems, liposomal delivery and polymeric matrices.Preparation of each type of CoQ-10 formulation would be within theknowledge of the person of skill in the art, although reference is madeto Remington's Pharmaceutical Sciences, 18th Edition (1990), thedisclosure of which is expressly incorporated herein by reference.

In a non-limiting example of a skin- or wound-care formulation, amedicated ointment base can be prepared with ingredients (% w/v) asfollows: Base (A) contains mineral oil USP (25%), microcrystalline wax(10%), cetyl alcohol (5%), mixed lanolin alcohols (10%), sorbitansesquioleate, (3%) and propyl p-(OH)-benzoate (0.1%). Base (B) containsglycerine (3%), methyl p-(OH)-benzoate (0.1%) and deionized water(43.8%). Bases (A) and (B) are heated separately to 75° C. and mixedwith gentle stirring while cooling to 45° C. to prepare the ointmentbase. In a non-limiting exemplary embodiment of the present invention,the CoQ-10/LF/AGN (2:20:1 premix) blend and the ointment base can bemixed to homogeneity at 1:5 ratios.

Example-16 Skin Cleansing Formulation

In another non-limiting example of a skin- or wound-care formulation, askin cleansing solution composition can be prepared. Formula for thebase solution is as follows, in which the values are given as % w/w ofthe total composition: water (81%), propylene glycol (5%), glycerin USP(5%), and polysorbate-20 (5%). The CoQ-10/LF/AGN (2:20:1 premix) blendcan be mixed slowly until completely dissolved until solution turnsuniform and clear. The solution may be further diluted by adding water.The skin cleansing solution with CoQ-10 blend can be applied to theinfected skin site by any suitable means such as cotton wool, cottonswab or the like.

In yet another non-limiting example of a skin- or wound-careformulation, a mild non-irritating skin crème base can be prepared asfollows: Oil phase (A) consists of cetearly alcohol (5%), silicone oil200 fluid (1%), isopropyl myristate (2%) and sodium stearoyl-2-lactylate(2%). Aqueous phase (B) consists of propylene glycol (5%), sodiumcitrate (0.2%) and purified water to make up to 100% w/v. The componentsof oil phase (A) are mixed at 65° C., and the components of aqueousphase (B) are mixed at 70° C. Aqueous phase (B) is added to oil phase(A) under cooling with moderate agitation. In an exemplary embodiment ofthe present invention, the CoQ-10/LF/AGN (2:20:1 premix) blend and theointment base can be mixed to homogeneity at a 1:10 ratio.

In yet another non-limiting example of a skin- or wound-careformulation, a makeup crème base can be prepared as following: Mixture(A) contains magnesium aluminum silicate (2.6%), sodium carboxy-methylcellulose (0.4%) and deionized water (42.4%). Mixture (B) contains adispersing agent (0.3%), propylene glycol (5.0%) and deionized water(12.3%). Mixture (C) contains talc (18.5%), kaolin (1.3%), titaniumdioxide (3.7%) and iron oxides, (1.5%). Mixture (D) contained isopropylmyristate (5.0%), strearyl alcohol (2.0%), lanolin absorption base(2.0%), sorbitan monolaurate (0.75%), polyoxyethylene (20) sorbitanmonolaurate (2.25%) and perfume. Solids of (A) are blended, added towater at 80° C. and stirred until smooth. Contents of (C) are pulverizedand added to (B) and passed through a colloid mill to yield a smoothpaste. Mixture of (B)+(C) is added to (A) and heated to 60-65° C. Thecontents of (D) are then heated to 70° C. and mixed with the (A)+(B)+(C)blend; stirred until the temperature reached 45° C., perfume is addedand mixed until cool. In an exemplary embodiment of the presentinvention, the CoQ-10/LF/AGN (2:20:1 premix) blend and the makeup crèmebase can be mixed to homogeneity at a 1:10 ratio.

In yet another non-limiting example of a skin- or wound-careformulation, an antiperspirant base can be prepared as follows: Oilphase (A) is prepared with mineral oil (23%), calciumstearoyl-2-lactylate (3.2%) and PEG 400 dioleate, (0.8%). Aqueous phase(B) contains glycerine (3%), 60% sodium lactate (10%) and purified water(20%). Mixture (C) contains 50% aluminum chlorohydrate (40%). Mixtures(A), (B) and (C) are separately heated at 70° C. Aqueous phase solution(B) is quickly added to (C) followed by mixing of (A) with moderateagitation while cooling. In an exemplary embodiment of the presentinvention, the CoQ-10/LF/AGN (2:20:1 premix) blend and theantiperspirant base can be mixed to homogeneity at a 1:10 ratio.

Example-17 Prophylactic Migraine Formulation

CoQ-10 has been shown to be effective to reduce the number and severityof migraine headaches in migraneurs when taken as a daily supplement.The following formulation combines CoQ-10 with other components known toreduce the number and severity of migraines, such as riboflavin, andmagnesium in a formulation that may be taken daily. The addition ofangiogenin promotes vascular health which is beneficial for preventionof vascular type headaches such as migraine. The formulation mayoptionally include feverfew at 20-80 mg/day, preferably about 50 mg/day.

TABLE 14 Ingredient Per Serving % DV Lactoferrin* 90 mg † CoQ-10 30 mg †Angiogenin* 30 mg † Calcium (from Citrate) 50 mg  10% Magnesium (fromOxide) 400 mg  100% Riboflavin 10 mg 500% Sodium Bicarbonate USP 10 mg †Citric acid 20 mg † Tyrosine 50 mg † *LF and AGN can be incorporated as120 mg (3:1) premix instead of individual ingredients.

A pharmaceutical composition of CoQ-10 blend can be prepared with theingredients listed in Table 14. Appropriate ratios of CoQ-10/LF/AGN andthe remaining actives were mixed to homogeneity and the composition isencapsulated in hydroxypropylmethyl cellulose (HPMC) two-piece capsulesaccording to methods commonly practiced in the art of manufacturing ofdietary supplements.

Formulations for Uro-Genital Health

The present invention also describes compositions and methods formaintaining uro-genital health, improving sexual function, improvingenergy, enhancing feelings of well-being and increasing muscle mass, byadministering CoQ-10/LF/ANG mixtures, in combination with other naturaland organic constituents.

Example-18 Formula for Male Virility and Enhancing Sexual Performance

The below-described composition with CoQ-10 blend, when administered canoptimize the inflow of sufficient blood to promote smooth musclerelaxation. The effect is sufficient in the corpus cavernosum to sustainsmooth muscle relaxation and thereby raise energy levels, improve sexualfunction, enhance feelings of well-being and increase muscle mass in thehuman male. Additional active ingredients can be added to achieveincidental benefits. For instance, saw palmetto is especially helpfulfor overcoming glandular weakness and to regenerate sexual glands. It isa well-known dietary aid for increasing male prostate health.

TABLE 15 Ingredient Per Serving % DV Coenzyme Q-10 30 mg †Lactoferrin-(tcr)* 90 mg † Angiogenin* 30 mg † Vitamin-B6 (a PyridoxineHCl) 4 mg 200% Vitamin-C (Ca-ascorbate) 60 mg 200% Vitamin-E (acetate)60 IU 200% Zinc (32% zinc citrate) 7.5 mg  50% Lecithin (granules) 30 mg† Damiana extract 25 mg † Sarsaparilla extract 25 mg † Saw Palmetto StdExtract (85% Fat) 25 mg † L-Theanine (decaffeinated)* 25 mg †Acetyl-L-carnitine 100 mg † L-Arginine HCl (81.6% ARG) 50 mg †L-Tyrosine 50 mg † Sodium bicarbonate 7.5 mg † *LF and AGN can beincorporated as 120 mg (3:1) premix instead of individual ingredients.

The above ingredients can be used to prepare capsules, or tablets.Lactose and corn starch are commonly used as diluents for capsules andas carriers for tablets. Lubricating agents, such as magnesium stearate,are typically added to form tablets. Additional inert ingredients may beadded as desired to achieve a desired taste, color or consistency.

Example-19 Formula for Female Libido and Enhancing Sexual Performance

Proper sexual functioning in women depends on the sexual response cycle,which consists of an anticipatory mental set (sexual motive state orstate of desire), effective vaso-congestive arousal (swelling andlubrication), orgasm, and resolution. In women, orgasm is accompanied bycontractions of the muscles of the outer third of the vagina. Orgasm isfollowed by resolution, a sense of general pleasure, well-being, andmuscular relaxation. During this phase, women may be able to respond toadditional stimulation almost immediately. To increase blood flow in thefemale genital tissue is also useful to improve sexual wellness. Thefollowing CoQ-10 blend provides a safe, natural way to preserve andmaintain sexual responsiveness, endurance and enjoyment.

TABLE 16 Ingredient Per Serving % DV Coenzyme Q-10 30 mg †Lactoferrin-(tcr)* 90 mg † Angiogenin* 30 mg † Lysozyme 10 mg †Cranberry Extract 25 mg † L-Theanine (decaffeinated) 50 mg † EchinaceaPurp. Root Extract 4:1 25 mg † Acetyl-L-carnitine 100 mg  † Tyrosine 50mg † Magnesium (as oxide)  4 mg 1% Potassium Phosphate (98% di-basic)  5mg † Sodium bicarbonate 10 mg † *LF and AGN can be incorporated as 120mg (3:1) premix instead of individual ingredients.

The above ingredients can be used to prepare capsules, or tablets.Lactose and corn starch are commonly used as diluents for capsules andas carriers for tablets. Lubricating agents, such as magnesium stearate,are typically added to form tablets. Additional inert ingredients may beadded as desired to achieve a desired taste, color or consistency.

Formulations for Brain Health & Stress Management

The present invention, CoQ-10 blend, in combination with organicnutrients is aimed at stimulating the brain to produce a positivepsychoactive effect for stress management. CoQ-10 blend, a powerfulbiological delivery medium, could enhance the bio-availability ofessential nutrients to the brain, to effectively maintain the mentalfitness.

In addition to CoQ-10, LF and AGN, the supplementary constituentsinclude phosphatidyl serine, phenylalanine, B-complex vitamins, vitaminC, vitamin E, taurine, choline, copper, chromium and bicarbonate. Theseconstituents are incorporated in an effervescent drink formulation asfollows:

Example-20 Effervescent Drink Mix (Powder Blend) for Brain Health &Stress Management

TABLE 17 Ingredient Per Serving % DV Coenzyme Q-10 60 mg †Lactoferrin-(tcr)* 90 mg † Angiogenin* 30 mg † Vitamin B1 (as ThiamineMono) 1.5 mg 100% Vitamin B2 (as Riboflavin) 3.4 mg 200% Vitamin B3 (asNiacinamide) 20 mg 100% Vitamin B5 (as Calcium Pantothenate) 25 mg 250%Vitamin B6 (as Pyridoxine HCl) 10 mg 500% Vitamin B12 (asCyanocobalamin) 15 mcg 250% Folic acid 200 mcg  50% Vitamin-C (CalciumL-ascorbate) 120 mg 200% Vitamin-E (d-Alpha-Tocopherol Acetate) 60 IU200% Phosphatidyl serine 100 mg † Phenylalanine 500 mg † Taurine 400 mg† Choline (as Dihydrogen citrate) 300 mg † Malic acid 200 mg † L-Glycine150 mg † L-theanine (decaffeinated) 25 mg † Aspartic acid 5.0 mg † Zinc(as Zinc Gluconate) 3.0 mg † Copper (76.7% Copper Oxide) 0.5 mg  25%Chromium (19% Chromium Chloride) 60 mcg  50% *LF and AGN can beincorporated as 120 mg (3:1) premix instead of individual ingredients.

Pharmaceutically acceptable excipients also contained in the abovenutritional drink composition include, but are not limited to,bicarbonate/citric acid mixture, fructose-DC, magnesium stearate,stearic acid with natural cherry flavor and natural red color and allthe ingredients were blended to a homogenous mixture. Other inertingredients may be added as required to achieve a desired taste, coloror consistency. For optimum results, the serving of the presentinvention should be taken at least an hour before the meal.

The primary active constituents have the following advantages:Phosphatidyl serine (PS), a phospholipid commonly found in both plantand animal foods, is a naturally derived brain nutrient. Oralsupplementation with PS benefits cognitive functions, particularly inadults in their mature years. The U.S. Food and Drug Administration(FDA) authorized two health claims for PS, the first claim “phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly”, andthe second claim, “phosphatidyl serine may reduce the risk of dementiain the elderly”.

The essential amino acid phenylalanine contained in the formulation isconverted by the brain into neurotransmitters (noradrenaline anddopamine) and neuromodulator (β-phenylethylamine) with the help ofcofactors folic acid, vitamin C, vitamin B-6 and copper. Taurine, thesulfur-containing amino acid in the formulation, is anotherneuromodulator that is important for the regulation of electricallyactive tissues (eg. brain and heart). Taurine also helps to promote amellow mood without sedation or tranquilization. Theanine, thepolyphenolic extract from green tea in the formulation, is a powerfulnatural antioxidant and a free radical scavenger. When this green teafree radical scavenging antioxidant enters the brain, a feeling ofwell-being results, which is a positive reinforcement of brain activity.

Finally, the induction of carbon-dioxide bubbles through the bicarbonateeffervescence could directly reach the brain. The CO₂ released in themouth could instantly diffuse into the nasopharyngeal tissue and rapidlycross the blood-brain barrier. This results the following two effects:i) the CO₂ causes vasodilation (increase in blood flow to and within thebrain), and ii) the CO₂ also increases the permeability of theblood-brain barrier, thereby transporting more nutrients. These effectscould make the onset of the psychoactive outcome more rapid and intense.

Formulations for Detoxification and Internal Cleansing

Human body encounters toxins from both internal and external sources ona regular basis. Fortunately, physiological systems such as the liver,kidneys, lungs, intestines, and blood work continuously to clean outevery cell, organ and tissue.

The colon is one of the primary organs involved in the body'sdetoxification process. Harmful substances such as bacteria, pesticides,food additives, environmental pollutants, drugs and chemicals arefiltered out by an internal detoxification process and eliminatedthrough the intestinal tract.

Example-21 Formula for Colon Cleansing

The body's first line of defense is a healthy colon. However, thisintestinal detoxification process can breakdown from: overexposure toenvironmental pollutants, food and water, poor diet, lack of adequatefiber, excessive alcohol and caffeine, high stress, lack of exercise,overuse of antibiotics and prescription medications. When the body'sinternal detoxification process breaks down, toxins circulate into thebloodstream instead of being eliminated through the colon, causeillness, digestive ailments and other serious health disorders. Thisproduces a state of toxicity and colon cleansing becomes one of the mostimportant steps in detoxification.

TABLE 18 Ingredients Per Serving % DV Lactoferrin*  90 mg † Angiogenin* 30 mg † Coenzyme Q10  30 mg † Vitamin-C  60 mg 100% Probiotic lacticacid bacteria 250 mg † Cascara Sagrada 125 mg † Peppermint (oil) 125 mg† Gingerol (oil) 125 mg † Fennel (oil) 125 mg † Chlorella 250 mg † *LFand AGN can be incorporated as 120 mg (3:1) premix instead of individualingredients.

An effective dosage of the formulations, as exemplified above, can beadministered in the form of a soft-gel or a two-piece capsule. Asuitable two-piece capsule that can hold liquid without any leakage canbe prepared by using proper sealant or by converting the liquid into aform which is either solid or semi-solid at room temperature.Embodiments of the invention are also directed to the use of the aboveformulation in an enema.

Besides the multifunctional health benefits of CoQ-10/LF/AGN blend, theprimary active constituents have the following advantages: Chlorellacontains over 19 amino acids, beta-carotene, potassium and othervaluable vitamins and minerals, and enzymes. It is a potent detoxifier,cell enhancer, and blood cleanser. Chlorella liquid extract is apowerful internal deodorant that reduces odors originating in thedigestive tract. Peppermint cleans and strengthens the entire body,especially the bowels. Fennel seed is used for colic, gas and intestinalproblems. It helps stabilize the nervous system, improves digestion, andhas a diuretic effect. Cascara Sagrada promotes peristaltic action(bowel movement) in the intestinal tract.

Probiotic lactic acid bacteria (LAB) are vital for a healthy bowel.These friendly bacteria synthesize nutrients in the intestinal tract,counteract harmful bacteria that disturb proper digestion andelimination as described in Naidu U.S. Pat. No. 6,797,266 B2, issuedSep. 28, 2004.

Probiotic LAB useful in embodiments of the present invention includephysiologically effective dosages of at least one LAB strain, typicallyin the form of a freeze-dried powder, emulsion or viable or non-viablecell preparation, selected from a group consisting of, but not limitedto, strains of bacteria of the genus Lactobacillus including L.acidophilus, L. amylovorus, L. animalis, L. bavaricus, L. brevis, L.bulgaricus, L. casei spp. casei, L. casei spp. rhamnosus, L. crispatus,L. delbrueckii ssp. lactis, L. eichmanni, L. fermentum, L. helveticus,L. jensenii, L. kefir, L. paracasei, L. pentosus, L. plantarum, L.reuteri, L. salivarius and L. sake; strains of bacteria of the genusLeuconostoc including Leu. cremoris and Leu. lactis; strains of bacteriaof the genus Bifidobacterium including B. adolescentis, B. animalis, B.bifidum, B. breve, B. infantis, B. longum, and B. thermophilum; strainsof bacteria of the genus Pediococcus including Ped. acidilactici andPed. pentosus; strains of bacteria of the genus Peptostreptococcusincluding Pep. assacharolyticus and Pep. productus; strains of bacteriaof the genus Propionibacterium including Pro. acidipropionici, Pro.freudenreichii, Pro. jensenii and Pro. theonii; strains of bacteria ofthe genus Streptococcus including Strep. cremoris, Strep. faecium,Strep. lactis, Strep. raffinolactis and Strep. thermophilus.

Dosages of probiotic bacteria contained in the compositions of thepresent invention comprise bacterial counts in the range of 10² to 10¹²colony forming units (for viable LAB) or microbial cells (for non-viableLAB). Optimal dosages of probiotic bacteria contained in thecompositions of the present invention comprise bacteria counts in therange of 10⁵ to 10¹⁰ colony forming units (for viable LAB) or microbialcells (for non-viable LAB). Colony forming units are defined as totalnumber of viable bacteria grown on agar medium.

Example-22 Formula for Liver Cleansing

TABLE 19 Ingredients Per Serving % DV Lactoferrin* 90 mg † Angiogenin*30 mg † Coenzyme Q10 30 mg † Vitamin C 60 mg 100% Vitamin E 30 IU 100%Lecithin 30 mg † Cysteine peption 500 mg † Milk Thistle 250 mg †Dandelion extract (1:1 in ethanol) 10 mg † *LF and AGN can beincorporated as 120 mg (3:1) premix instead of individual ingredients.

Besides the multifunctional health benefits of CoQ-10/LF/AGN blend, theprimary active constituents have the following advantages: Milk Thistleinhibits the enzyme, lipoxygenase, thereby prevents the formation ofleukotrienes that are responsible for inflammations. It also preventsfree radical damage to liver cells and stimulates the production of newliver cells. Milk Thistle helps protect normal liver function fromdamage by alcohol, environmental stress, and other toxic substances.Another potent liver detoxificant is dandelion. It stimulates the liverto detoxify poisons, promotes healthy circulation, and strengthens weakarteries. Dandelion (Taraxacum officinale) above ground parts (1:1 in25% alcohol) is a promoter of healthy circulation, skin toner, and bloodvessel cleanser.

Example-23 Formula for Blood Cleansing

TABLE 20 Ingredients Per Serving % DV Lactoferrin* 90 mg † Angiogenin*30 mg † Coenzyme Q10 30 mg † Vitamin-C 60 mg 100% Turmeric root extract30 mg † Burdock root extract 250 mg  † Rosemary leaf extract 250 mg  †Red Clover extract 50 mg † Yarrow (1:1 ethanol extract) 10 mg † *LF andAGN can be incorporated as 120 mg (3:1) premix instead of individualingredients.

All ingredients from Table 20 can be compressed into a tablet form.Pharmaceutically acceptable excipients including fructose-DC, magnesiumstearate, stearic acid, CanTab (tableting dextrose, Penford FoodIngredients, Englewood, Colo.), natural cherry flavor and natural bluecolor were blended with the ingredients from Table 20. Each of the aboveingredients was placed, in powdered form, into a commercial blender,mixed and, if necessary, passed through a mesh screen to removeaggregates. After 20 minutes of thorough mixing, the composition is coldpressed in a tablet press set at a maximum pressure of 6.4 tons yieldingchewable tablets.

The primary active constituents have the following advantages: Burdockroot extract is one of the best blood purifiers. It also reducesswelling around joints, dissolves calcification deposits, and clearsblood of harmful acids. Red Clover is also a very strong blood purifier.It is used as a tonic for the nerves and as a sedative for nervousexhaustion. Yarrow acts as a blood cleanser, opens the pores to permitfree perspiration for elimination of waste, relieving the kidneys. Italso helps to regulate the function of the liver, tones the mucousmembranes of the stomach and bowel, and heals the glandular system.

Example-24 Powdered Drink Formula for Cleansing of Respiratory Tract

TABLE 21 Ingredients Per Serving % DV Lactoferrin* 90 mg † Angiogenin*30 mg † Coenzyme Q10 30 mg † Vitamin-C 60 mg 100% Echinacea 1.0 g †Elder 1.0 g † Ginger root extract 0.5 g † Golden seal 0.5 g † Peppermint0.5 g † *LF and AGN can be incorporated as 120 mg (3:1) premix insteadof individual ingredients.

Example-25 Powdered Drink Formula for Cleansing of the Urinary Tract

TABLE 22 Ingredients Per Serving % DV Lactoferrin* 90 † Angiogenin* 30 †Coenzyme Q10 30 † Vitamin-C 60 100% Echinacea root extract 0.5 g †Golden seal root extract 0.5 g † Grapefruit seed extract 0.5 g †Licorice root extract 1.0 g † Cranberry extract 100 mg † L-theanine(decaffeinated) 25 mg † *LF and AGN can be incorporated as 120 mg (3:1)premix instead of individual ingredients.

For the above powdered drink formulae from Tables 21 and 22, may alsocontain pharmaceutically acceptable excipients including, but are notlimited to, bicarbonate/citric acid mixtures, fructose-DC, magnesiumstearate, stearic acid with flavor and color (natural or synthetic, asrequired). All the ingredients are blended to a homogenous mixture. Thisformulation may be prepared as a powder to be added to milk, water,yogurt or other food substance as a nutritional supplement.

It will be understood by those of skill in the art that numerous andvarious modifications can be made without departing from the spirit ofthe present invention.

Therefore, it should be clearly understood that the forms of the presentinvention are illustrative only and are not intended to limit the scopeof the present invention.

What is claimed is:
 1. A composition comprising isolated lactoferrin(LF) and isolated angiogenin (AGN) in a LF:AGN wt/wt ratio of from 50:1to 9:1, wherein the concentration of LF is 10-25 wt % and wherein theconcentration of AGN is 0.5-10 wt % in the composition and wherein theLF is complexed to a metal selected from the group consisting of zinc,copper, manganese, chromium, aluminum and gallium.
 2. The composition ofclaim 1, wherein the lactoferrin is combined with an anionic compoundselected from the group consisting of a carbonate, a bicarbonate, and acarbonated liquid.
 3. The composition of claim 2, wherein the anioniccompound is a bicarbonate.
 4. The composition of claim 1, wherein the LFis complexed to copper.
 5. The composition of claim 1, wherein the ratioof LF : AGN ranges between 20:1 to 9:1.
 6. The composition of claim 1,further comprising an oil, a suspending agent, a flavoring agent,coloring agents or combinations thereof.
 7. The composition of claim 6,wherein the oil is one or more selected from the group consisting ofseed oil, fish or marine oil, canola oil, vegetable oil, safflower oil,sunflower oil, nasturtium seed oil, mustard seed oil, olive oil, sesameoil, soybean oil, corn oil, peanut oil, cottonseed oil, rice bran oil,palm oil, rapeseed oil, palm kernel oil, lupin oil, coconut oil,flaxseed oil, and evening primrose oil.
 8. The composition of claim 1,further comprising a compound selected from the group consisting ofphospholipids, antioxidants, vitamins, amino acids, proteins, essentialminerals, lecithin and combinations thereof.
 9. The composition of claim8, wherein the composition further comprises L-carnitine,acetyl-L-carnitine or propionyl L-carnitine in an amount of 1% to 50% byweight.
 10. The composition of claim 8, wherein the phospholipid is oneor more selected from the group consisting of Docosahexaenoic acid(DHA), phosphatidyl glycerol, phosphatidyl inositol, phosphatidylserine, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidicacids, ceramides, cerebrosides, sphingomyelins and cardiolipins.
 11. Thecomposition of claim 8, wherein the vitamin is one or more selected fromthe group consisting of vitamin A, thiamine, niacinamide, pyridoxine,riboflavin, cyanocobalamin, biotin, pantothenic acid, vitamin C, vitaminD, vitamin E, vitamin K and folic acid.
 12. The composition of claim 8,wherein the mineral is one or more selected from the group consisting ofiron, calcium, magnesium, sodium, potassium, copper, chromium, zinc,molybdenum, iodine, boron, selenium, manganese, and combinationsthereof.
 13. The composition of claim 8, wherein lecithin is present inan amount of 10% to 60% by weight.
 14. The composition of claim 1,further comprising a viable or a non-viable probiotic selected from thegroup consisting of L. acidophilus, L. amylovorus, L. animalis, L.bavaricus, L. brevis, L. bulgaricus, L. casei spp. casei, L. casei spp.rhamnosus, L. crispatus, L. delbrueckii ssp. lactis, L. eichmanni, L.fermentum, L. helveticus, L. jensenii, L. kefir, L. paracasei, L.pentosus, L. plantarum, L. reuteri, L. sahvarius, L. sake, Leu.cremoris, Leu. lactis; B. adolescentis, B. animalis, B. bifidum, B.breve, B. infantis, B. longum, and B. thermophilum; Ped. acidilactici,Ped. pentosus, Pep. assacharolyticus, Pep. productus; Pro.acidipropionici, Pro. freudenreichii, Pro. jensenii, Pro. theonii,Strep. cremoris, Strep. faecium, Strep. lactis, Strep. raffinolactis andStrep. thermophilus.
 15. A formulation comprising the composition ofclaim 1, wherein the formulation further comprises S-adenosylmethionine.16. A formulation comprising the composition of claim 1, wherein theformulation further comprises, at least two of the followingingredients: chondroitin sulfate, glucosamine sulfate,methylsulfonylmethane, dimethylglycine, orcerasomal-cis-9-cetylmyristoleate.
 17. A carbonated beverage comprisingthe composition of claim
 1. 18. A composition according to claim 1,wherein said isolated lactoferrin and isolated angiogenin are obtainedfrom a LF:AGN premix prepared by a method comprising: isolating aLF-enriched fraction from a dairy, a non-dairy or a recombinant source;isolating an AGN-enriched fraction from a dairy, a non-dairy or arecombinant source; combining the LF-enriched fraction with theAGN-enriched fraction; freeze-drying or spray-drying the combinedfractions; and milling the freeze-dried or spray-dried combinedfractions to obtain a LF:AGN premix.
 19. The composition of claim 1,wherein the LF is complexed to zinc.